Daily Papers

In this paper, we address the challenging task of multimodal mathematical reasoning by incorporating the ability of ``slow thinking" into multimodal large language models (MLLMs). Contrary to existing methods that rely on direct or fast thinking, our key idea is to construct long chains of thought (CoT) consisting of atomic actions in a step-by-step manner, guiding MLLMs to perform complex reasoning. To this end, we design a novel AtomThink framework composed of three key modules: (i) a CoT annotation engine that automatically generates high-quality CoT annotations to address the lack of high-quality visual mathematical data; (ii) an atomic step fine-tuning strategy that jointly optimizes an MLLM and a policy reward model (PRM) for step-wise reasoning; and (iii) four different search strategies that can be applied with the PRM to complete reasoning. Additionally, we propose AtomMATH, a large-scale multimodal dataset of long CoTs, and an atomic capability evaluation metric for mathematical tasks. Extensive experimental results show that the proposed AtomThink significantly improves the performance of baseline MLLMs, achieving approximately 50\% relative accuracy gains on MathVista and 120\% on MathVerse. To support the advancement of multimodal slow-thinking models, we will make our code and dataset publicly available on https://github.com/Quinn777/AtomThink.

In this paper, we address the challenging task of multimodal mathematical reasoning by incorporating the ability of "slow thinking" into multimodal large language models (MLLMs). Our core idea is that different levels of reasoning abilities can be combined dynamically to tackle questions with different complexity. To this end, we propose a paradigm of Self-structured Chain of Thought (SCoT), which is composed of minimal semantic atomic steps. Different from existing methods that rely on structured templates or free-form paradigms, our method can not only generate cognitive CoT structures for various complex tasks but also mitigates the phenomenon of overthinking. To introduce structured reasoning capabilities into visual understanding models, we further design a novel AtomThink framework with four key modules, including (i) a data engine to generate high-quality multimodal reasoning paths; (ii) a supervised fine-tuning process with serialized inference data; (iii) a policy-guided multi-turn inference method; and (iv) an atomic capability metric to evaluate the single step utilization rate. We conduct extensive experiments to show that the proposed AtomThink significantly improves the performance of baseline MLLMs, achieving more than 10\% average accuracy gains on MathVista and MathVerse. Compared to state-of-the-art structured CoT approaches, our method not only achieves higher accuracy but also improves data utilization by 5 times and boosts inference efficiency by 85.3\%. Our code is now public available in https://github.com/Quinn777/AtomThink.

Modeling the energy and forces of atomic systems is a fundamental problem in computational chemistry with the potential to help address many of the world's most pressing problems, including those related to energy scarcity and climate change. These calculations are traditionally performed using Density Functional Theory, which is computationally very expensive. Machine learning has the potential to dramatically improve the efficiency of these calculations from days or hours to seconds. We propose the Spherical Channel Network (SCN) to model atomic energies and forces. The SCN is a graph neural network where nodes represent atoms and edges their neighboring atoms. The atom embeddings are a set of spherical functions, called spherical channels, represented using spherical harmonics. We demonstrate, that by rotating the embeddings based on the 3D edge orientation, more information may be utilized while maintaining the rotational equivariance of the messages. While equivariance is a desirable property, we find that by relaxing this constraint in both message passing and aggregation, improved accuracy may be achieved. We demonstrate state-of-the-art results on the large-scale Open Catalyst dataset in both energy and force prediction for numerous tasks and metrics.

Large language models (LLMs) such as generative pretrained transformers (GPTs) have shown potential for various commercial applications, but their applicability for materials design remains underexplored. In this article, we introduce AtomGPT, a model specifically developed for materials design based on transformer architectures, to demonstrate the capability for both atomistic property prediction and structure generation. We show that a combination of chemical and structural text descriptions can efficiently predict material properties with accuracy comparable to graph neural network models, including formation energies, electronic bandgaps from two different methods and superconducting transition temperatures. Furthermore, we demonstrate that AtomGPT can generate atomic structures for tasks such as designing new superconductors, with the predictions validated through density functional theory calculations. This work paves the way for leveraging LLMs in forward and inverse materials design, offering an efficient approach to the discovery and optimization of materials.

Large Language Models (LLMs) achieve superior performance through training-time scaling, and test-time scaling further enhances their capabilities by conducting effective reasoning during inference. However, as the scale of reasoning increases, existing test-time scaling methods suffer from accumulated historical information, which not only wastes computational resources but also interferes with effective reasoning. To address this issue, we observe that complex reasoning progress is often achieved by solving a sequence of independent subquestions, each being self-contained and verifiable. These subquestions are essentially atomic questions, relying primarily on their current state rather than accumulated history, similar to the memoryless transitions in a Markov process. Based on this observation, we propose Atom of Thoughts (AoT), where each state transition in the reasoning process consists of decomposing the current question into a dependency-based directed acyclic graph and contracting its subquestions, forming a new atomic question state. This iterative decomposition-contraction process continues until reaching directly solvable atomic questions, naturally realizing Markov transitions between question states. Furthermore, these atomic questions can be seamlessly integrated into existing test-time scaling methods, enabling AoT to serve as a plug-in enhancement for improving reasoning capabilities. Experiments across six benchmarks demonstrate the effectiveness of AoT both as a standalone framework and a plug-in enhancement. Notably, on HotpotQA, when applied to gpt-4o-mini, AoT achieves an 80.6% F1 score, surpassing o3-mini by 3.4% and DeepSeek-R1 by 10.6%. The code will be available at https://github.com/qixucen/atom.

Materials synthesis is vital for innovations such as energy storage, catalysis, electronics, and biomedical devices. Yet, the process relies heavily on empirical, trial-and-error methods guided by expert intuition. Our work aims to support the materials science community by providing a practical, data-driven resource. We have curated a comprehensive dataset of 17K expert-verified synthesis recipes from open-access literature, which forms the basis of our newly developed benchmark, AlchemyBench. AlchemyBench offers an end-to-end framework that supports research in large language models applied to synthesis prediction. It encompasses key tasks, including raw materials and equipment prediction, synthesis procedure generation, and characterization outcome forecasting. We propose an LLM-as-a-Judge framework that leverages large language models for automated evaluation, demonstrating strong statistical agreement with expert assessments. Overall, our contributions offer a supportive foundation for exploring the capabilities of LLMs in predicting and guiding materials synthesis, ultimately paving the way for more efficient experimental design and accelerated innovation in materials science.

Large Language Models exhibit impressive reasoning capabilities across diverse tasks, motivating efforts to distill these capabilities into smaller models through generated reasoning data. However, direct training on such synthesized reasoning data may lead to superficial imitation of reasoning process, rather than fostering a genuine integration of reasoning capabilities with underlying knowledge. To address this, we propose TinyThinker, a framework introducing two novel approaches. First, we introduce a three-stage process that incrementally guides the student model through the reasoning process, progressively refining knowledge from coarse to fine granularity. Second, we develop a two-phase training framework comprising an initial reasoning acquisition phase followed by a self-reflection phase utilizing self-generated data. Experiments on commonsense reasoning benchmarks demonstrate that TinyThinker achieves superior performance compared to baselines. Ablation studies further validate the effectiveness of each component in our framework. TinyThinker is extendable to other knowledge-intensive reasoning tasks, offering an alternative strategy for developing effective reasoning capabilities in smaller language models. Codes are available at https://github.com/shengminp/TinyThinker

Supervised fine-tuning with synthesized instructions has been a common practice for adapting LLMs to domain-specific QA tasks. However, the synthesized instructions deviate from real user questions and expected answers. This study proposes a novel framework called DeepThink to generate high-quality instructions. DeepThink first generates a few seed questions to mimic actual user questions, simulates conversations to uncover the hidden user needs, and refines the answer by conversational contexts and the retrieved documents for more comprehensive answers. Experiments demonstrate that DeepThink achieves an average performance improvement of 7.92% compared to a GPT-4-turbo+RAG-based assistant on the real user test set in the advertising domain across dimensions such as relevance, completeness, clarity, accuracy, and actionability.

Machine-learned force fields have transformed the atomistic modelling of materials by enabling simulations of ab initio quality on unprecedented time and length scales. However, they are currently limited by: (i) the significant computational and human effort that must go into development and validation of potentials for each particular system of interest; and (ii) a general lack of transferability from one chemical system to the next. Here, using the state-of-the-art MACE architecture we introduce a single general-purpose ML model, trained on a public database of 150k inorganic crystals, that is capable of running stable molecular dynamics on molecules and materials. We demonstrate the power of the MACE-MP-0 model -- and its qualitative and at times quantitative accuracy -- on a diverse set problems in the physical sciences, including the properties of solids, liquids, gases, and chemical reactions. The model can be applied out of the box and as a starting or "foundation model" for any atomistic system of interest and is thus a step towards democratising the revolution of ML force fields by lowering the barriers to entry.

Machine learning potentials (MLPs) trained on accurate quantum chemical data can retain the high accuracy, while inflicting little computational demands. On the downside, they need to be trained for each individual system. In recent years, a vast number of MLPs has been trained from scratch because learning additional data typically requires to train again on all data to not forget previously acquired knowledge. Additionally, most common structural descriptors of MLPs cannot represent efficiently a large number of different chemical elements. In this work, we tackle these problems by introducing element-embracing atom-centered symmetry functions (eeACSFs) which combine structural properties and element information from the periodic table. These eeACSFs are a key for our development of a lifelong machine learning potential (lMLP). Uncertainty quantification can be exploited to transgress a fixed, pre-trained MLP to arrive at a continuously adapting lMLP, because a predefined level of accuracy can be ensured. To extend the applicability of an lMLP to new systems, we apply continual learning strategies to enable autonomous and on-the-fly training on a continuous stream of new data. For the training of deep neural networks, we propose the continual resilient (CoRe) optimizer and incremental learning strategies relying on rehearsal of data, regularization of parameters, and the architecture of the model.

Graph Neural Networks (GNNs) have been widely adopted for drug discovery with molecular graphs. Nevertheless, current GNNs are mainly good at leveraging short-range interactions (SRI) but struggle to capture long-range interactions (LRI), both of which are crucial for determining molecular properties. To tackle this issue, we propose a method that implicitly projects all original atoms into a few Neural Atoms, which abstracts the collective information of atomic groups within a molecule. Specifically, we explicitly exchange the information among neural atoms and project them back to the atoms' representations as an enhancement. With this mechanism, neural atoms establish the communication channels among distant nodes, effectively reducing the interaction scope of arbitrary node pairs into a single hop. To provide an inspection of our method from a physical perspective, we reveal its connection with the traditional LRI calculation method, Ewald Summation. We conduct extensive experiments on three long-range graph benchmarks, covering both graph-level and link-level tasks on molecular graphs. We empirically justify that our method can be equipped with an arbitrary GNN and help to capture LRI.

Large language models (LLMs) have shown remarkable performance in complex reasoning tasks, but their efficiency is hindered by the substantial memory and computational costs associated with generating lengthy tokens. In this paper, we propose LightThinker, a novel method that enables LLMs to dynamically compress intermediate thoughts during reasoning. Inspired by human cognitive processes, LightThinker compresses verbose thought steps into compact representations and discards the original reasoning chains, thereby significantly reducing the number of tokens stored in the context window. This is achieved by training the model on when and how to perform compression through data construction, mapping hidden states to condensed gist tokens, and creating specialized attention masks. Additionally, we introduce the Dependency (Dep) metric to quantify the degree of compression by measuring the reliance on historical tokens during generation. Extensive experiments on four datasets and two models show that LightThinker reduces peak memory usage and inference time, while maintaining competitive accuracy. Our work provides a new direction for improving the efficiency of LLMs in complex reasoning tasks without sacrificing performance. Code will be released at https://github.com/zjunlp/LightThinker.

In most current research, large language models (LLMs) are able to perform reasoning tasks by generating chains of thought through the guidance of specific prompts. However, there still exists a significant discrepancy between their capability in solving complex reasoning problems and that of humans. At present, most approaches focus on chains of thought (COT) and tool use, without considering the adoption and application of human cognitive frameworks. It is well-known that when confronting complex reasoning challenges, humans typically employ various cognitive abilities, and necessitate interaction with all aspects of tools, knowledge, and the external environment information to accomplish intricate tasks. This paper introduces a novel intelligent framework, referred to as OlaGPT. OlaGPT carefully studied a cognitive architecture framework, and propose to simulate certain aspects of human cognition. The framework involves approximating different cognitive modules, including attention, memory, reasoning, learning, and corresponding scheduling and decision-making mechanisms. Inspired by the active learning mechanism of human beings, it proposes a learning unit to record previous mistakes and expert opinions, and dynamically refer to them to strengthen their ability to solve similar problems. The paper also outlines common effective reasoning frameworks for human problem-solving and designs Chain-of-Thought (COT) templates accordingly. A comprehensive decision-making mechanism is also proposed to maximize model accuracy. The efficacy of OlaGPT has been stringently evaluated on multiple reasoning datasets, and the experimental outcomes reveal that OlaGPT surpasses state-of-the-art benchmarks, demonstrating its superior performance. Our implementation of OlaGPT is available on GitHub: https://github.com/oladata-team/OlaGPT.

Research on LLM technologies is rapidly emerging, with most of them employing a 'fast thinking' approach to inference. Most LLMs generate the final result based solely on a single query and LLM's reasoning capabilities. However, with the advent of OpenAI-o1, 'slow thinking' techniques have garnered increasing attention because its process is closer to the human thought process. Inspired by the human ability to constantly associate and replenish knowledge during thinking, we developed the novel Chain-of-Associated-Thoughts (CoAT) framework, which introduces an innovative synergy between the Monte Carlo Tree Search (MCTS) algorithm and a dynamic mechanism for integrating new key information, termed 'associative memory'. By combining the structured exploration capabilities of MCTS with the adaptive learning capacity of associative memory, CoAT significantly expands the LLM search space, enabling our framework to explore diverse reasoning pathways and dynamically update its knowledge base in real-time. This allows the framework to not only revisit and refine earlier inferences but also adaptively incorporate evolving information, ensuring that the final output is both accurate and comprehensive. To validate the effectiveness of our framework, we conducted extensive experiments across a range of generative and reasoning tasks. These experiments demonstrated that our framework outperforms conventional inference processes on accuracy, coherence, and diversity. The framework's ability to iteratively expand its search space while retaining contextually relevant information results.

Reducing hallucination of Large Language Models (LLMs) is imperative for use in the sciences where reproducibility is crucial. However, LLMs inherently lack long-term memory, making it a nontrivial, ad hoc, and inevitably biased task to fine-tune them on domain-specific literature and data. Here we introduce LLaMP, a multimodal retrieval-augmented generation (RAG) framework of multiple data-aware reasoning-and-acting (ReAct) agents that dynamically interact with computational and experimental data on Materials Project (MP). Without fine-tuning, LLaMP demonstrates an ability to comprehend and integrate various modalities of materials science concepts, fetch relevant data stores on the fly, process higher-order data (such as crystal structures and elastic tensors), and summarize multi-step procedures for solid-state synthesis. We show that LLaMP effectively corrects errors in GPT-3.5's intrinsic knowledge, reducing a 5.21% MAPE on frequently-documented bandgaps and a significant 1103.54% MAPE on formation energies -- errors that GPT-3.5 seems to derive from mixed data sources. Additionally, LLaMP substantially reduces the hallucinated volumetric strain in a diamond cubic silicon structure from 66.3% to 0. The proposed framework offers an intuitive and nearly hallucination-free approach to exploring materials informatics and establishes a pathway for knowledge distillation and fine-tuning other language models. We envision the framework as a valuable component for scientific hypotheses and a foundation for future autonomous laboratories where multiple LLM agents communicate and cooperate with robotics to drive material synthesis and chemical reactions without hard-coded human logic and intervention.

Recent advancements in large language models (LLMs) have led to significant improvements in various natural language processing tasks, but it is still challenging for LLMs to perform knowledge-intensive complex question answering due to LLMs' inefficacy in reasoning planning and the hallucination problem. A typical solution is to employ retrieval-augmented generation (RAG) coupled with chain-of-thought (CoT) reasoning, which decomposes complex questions into chain-like sub-questions and applies iterative RAG at each sub-question. However, prior works exhibit sub-optimal reasoning planning and overlook dynamic knowledge retrieval from heterogeneous sources. In this paper, we propose AtomR, a novel heterogeneous knowledge reasoning framework that conducts multi-source reasoning at the atomic level. Drawing inspiration from the graph modeling of knowledge, AtomR leverages large language models (LLMs) to decompose complex questions into combinations of three atomic knowledge operators, significantly enhancing the reasoning process at both the planning and execution stages. We also introduce BlendQA, a novel evaluation benchmark tailored to assess complex heterogeneous knowledge reasoning. Experiments show that AtomR significantly outperforms state-of-the-art baselines across three single-source and two multi-source reasoning benchmarks, with notable performance gains of 9.4% on 2WikiMultihop and 9.5% on BlendQA.

Logical reasoning task has attracted great interest since it was proposed. Faced with such a task, current competitive models, even large language models (e.g., ChatGPT and PaLM 2), still perform badly. Previous promising LMs struggle in logical consistency modeling and logical structure perception. To this end, we model the logical reasoning task by transforming each logical sample into reasoning paths and propose an architecture PathReasoner. It addresses the task from the views of both data and model. To expand the diversity of the logical samples, we propose an atom extension strategy supported by equivalent logical formulas, to form new reasoning paths. From the model perspective, we design a stack of transformer-style blocks. In particular, we propose a path-attention module to joint model in-atom and cross-atom relations with the high-order diffusion strategy. Experiments show that PathReasoner achieves competitive performances on two logical reasoning benchmarks and great generalization abilities.

Recent years have witnessed a surge in the development of protein foundation models, significantly improving performance in protein prediction and generative tasks ranging from 3D structure prediction and protein design to conformational dynamics. However, the capabilities and limitations associated with these models remain poorly understood due to the absence of a unified evaluation framework. To fill this gap, we introduce ProteinBench, a holistic evaluation framework designed to enhance the transparency of protein foundation models. Our approach consists of three key components: (i) A taxonomic classification of tasks that broadly encompass the main challenges in the protein domain, based on the relationships between different protein modalities; (ii) A multi-metric evaluation approach that assesses performance across four key dimensions: quality, novelty, diversity, and robustness; and (iii) In-depth analyses from various user objectives, providing a holistic view of model performance. Our comprehensive evaluation of protein foundation models reveals several key findings that shed light on their current capabilities and limitations. To promote transparency and facilitate further research, we release the evaluation dataset, code, and a public leaderboard publicly for further analysis and a general modular toolkit. We intend for ProteinBench to be a living benchmark for establishing a standardized, in-depth evaluation framework for protein foundation models, driving their development and application while fostering collaboration within the field.

This work addresses the challenge of democratizing advanced Large Language Models (LLMs) by compressing their mathematical reasoning capabilities into sub-billion parameter Small Language Models (SLMs) without compromising performance. We introduce Equation-of-Thought Distillation (EoTD), a novel technique that encapsulates the reasoning process into equation-based representations to construct an EoTD dataset for fine-tuning SLMs. Additionally, we propose the Mix Thoughts Distillation (MTD) framework to enhance the reasoning performance of SLMs. This involves creating a reasoning dataset with multiple thought processes and using it for fine-tuning. Our experimental findings demonstrate that EoTD significantly boosts the reasoning abilities of SLMs, while MTD enables these models to achieve state-of-the-art reasoning performance.

Supervised machine learning approaches have been increasingly used in accelerating electronic structure prediction as surrogates of first-principle computational methods, such as density functional theory (DFT). While numerous quantum chemistry datasets focus on chemical properties and atomic forces, the ability to achieve accurate and efficient prediction of the Hamiltonian matrix is highly desired, as it is the most important and fundamental physical quantity that determines the quantum states of physical systems and chemical properties. In this work, we generate a new Quantum Hamiltonian dataset, named as QH9, to provide precise Hamiltonian matrices for 999 or 2998 molecular dynamics trajectories and 130,831 stable molecular geometries, based on the QM9 dataset. By designing benchmark tasks with various molecules, we show that current machine learning models have the capacity to predict Hamiltonian matrices for arbitrary molecules. Both the QH9 dataset and the baseline models are provided to the community through an open-source benchmark, which can be highly valuable for developing machine learning methods and accelerating molecular and materials design for scientific and technological applications. Our benchmark is publicly available at https://github.com/divelab/AIRS/tree/main/OpenDFT/QHBench.

The adaptation of large language models (LLMs) to chemistry has shown promising performance in molecular understanding tasks, such as generating a text description from a molecule. However, proper reasoning based on molecular structural information remains a significant challenge, e.g., even advanced LLMs such as GPT-4o struggle to identify functional groups which are crucial for inferring the molecular property of interest. To address this limitation, we propose StructCoT, a structure-aware chain-of-thought (CoT) that enhances LLMs' understanding of molecular structures by explicitly injecting the key structural features of molecules. Moreover, we introduce two fine-tuning frameworks for adapting the existing LLMs to use our StructCoT. Our experiments demonstrate that incorporating StructCoT with our fine-tuning frameworks leads to consistent improvements in both molecular understanding tasks.

Graph neural networks are emerging as promising methods for modeling molecular graphs, in which nodes and edges correspond to atoms and chemical bonds, respectively. Recent studies show that when 3D molecular geometries, such as bond lengths and angles, are available, molecular property prediction tasks can be made more accurate. However, computing of 3D molecular geometries requires quantum calculations that are computationally prohibitive. For example, accurate calculation of 3D geometries of a small molecule requires hours of computing time using density functional theory (DFT). Here, we propose to predict the ground-state 3D geometries from molecular graphs using machine learning methods. To make this feasible, we develop a benchmark, known as Molecule3D, that includes a dataset with precise ground-state geometries of approximately 4 million molecules derived from DFT. We also provide a set of software tools for data processing, splitting, training, and evaluation, etc. Specifically, we propose to assess the error and validity of predicted geometries using four metrics. We implement two baseline methods that either predict the pairwise distance between atoms or atom coordinates in 3D space. Experimental results show that, compared with generating 3D geometries with RDKit, our method can achieve comparable prediction accuracy but with much smaller computational costs. Our Molecule3D is available as a module of the MoleculeX software library (https://github.com/divelab/MoleculeX).

We introduce SELF-DISCOVER, a general framework for LLMs to self-discover the task-intrinsic reasoning structures to tackle complex reasoning problems that are challenging for typical prompting methods. Core to the framework is a self-discovery process where LLMs select multiple atomic reasoning modules such as critical thinking and step-by-step thinking, and compose them into an explicit reasoning structure for LLMs to follow during decoding. SELF-DISCOVER substantially improves GPT-4 and PaLM 2's performance on challenging reasoning benchmarks such as BigBench-Hard, grounded agent reasoning, and MATH, by as much as 32% compared to Chain of Thought (CoT). Furthermore, SELF-DISCOVER outperforms inference-intensive methods such as CoT-Self-Consistency by more than 20%, while requiring 10-40x fewer inference compute. Finally, we show that the self-discovered reasoning structures are universally applicable across model families: from PaLM 2-L to GPT-4, and from GPT-4 to Llama2, and share commonalities with human reasoning patterns.

We present ControlLLM, a novel framework that enables large language models (LLMs) to utilize multi-modal tools for solving complex real-world tasks. Despite the remarkable performance of LLMs, they still struggle with tool invocation due to ambiguous user prompts, inaccurate tool selection and parameterization, and inefficient tool scheduling. To overcome these challenges, our framework comprises three key components: (1) a task decomposer that breaks down a complex task into clear subtasks with well-defined inputs and outputs; (2) a Thoughts-on-Graph (ToG) paradigm that searches the optimal solution path on a pre-built tool graph, which specifies the parameter and dependency relations among different tools; and (3) an execution engine with a rich toolbox that interprets the solution path and runs the tools efficiently on different computational devices. We evaluate our framework on diverse tasks involving image, audio, and video processing, demonstrating its superior accuracy, efficiency, and versatility compared to existing methods.

Applications of machine learning techniques for materials modeling typically involve functions known to be equivariant or invariant to specific symmetries. While graph neural networks (GNNs) have proven successful in such tasks, they enforce symmetries via the model architecture, which often reduces their expressivity, scalability and comprehensibility. In this paper, we introduce (1) a flexible framework relying on stochastic frame-averaging (SFA) to make any model E(3)-equivariant or invariant through data transformations. (2) FAENet: a simple, fast and expressive GNN, optimized for SFA, that processes geometric information without any symmetrypreserving design constraints. We prove the validity of our method theoretically and empirically demonstrate its superior accuracy and computational scalability in materials modeling on the OC20 dataset (S2EF, IS2RE) as well as common molecular modeling tasks (QM9, QM7-X). A package implementation is available at https://faenet.readthedocs.io.

The sequential process of conceptualization and instantiation is essential to generalizable commonsense reasoning as it allows the application of existing knowledge to unfamiliar scenarios. However, existing works tend to undervalue the step of instantiation and heavily rely on pre-built concept taxonomies and human annotations to collect both types of knowledge, resulting in a lack of instantiated knowledge to complete reasoning, high cost, and limited scalability. To tackle these challenges, we introduce CANDLE, a distillation framework that iteratively performs contextualized conceptualization and instantiation over commonsense knowledge bases by instructing large language models to generate both types of knowledge with critic filtering. By applying CANDLE to ATOMIC, we construct a comprehensive knowledge base comprising six million conceptualizations and instantiated commonsense knowledge triples. Both types of knowledge are firmly rooted in the original ATOMIC dataset, and intrinsic evaluations demonstrate their exceptional quality and diversity. Empirical results indicate that distilling CANDLE on student models provides benefits across four downstream tasks. Our code, data, and models are publicly available at https://github.com/HKUST-KnowComp/CANDLE.

Innovations like protein diffusion have enabled significant progress in de novo protein design, which is a vital topic in life science. These methods typically depend on protein structure encoders to model residue backbone frames, where atoms do not exist. Most prior encoders rely on atom-wise features, such as angles and distances between atoms, which are not available in this context. Thus far, only several simple encoders, such as IPA, have been proposed for this scenario, exposing the frame modeling as a bottleneck. In this work, we proffer the Vector Field Network (VFN), which enables network layers to perform learnable vector computations between coordinates of frame-anchored virtual atoms, thus achieving a higher capability for modeling frames. The vector computation operates in a manner similar to a linear layer, with each input channel receiving 3D virtual atom coordinates instead of scalar values. The multiple feature vectors output by the vector computation are then used to update the residue representations and virtual atom coordinates via attention aggregation. Remarkably, VFN also excels in modeling both frames and atoms, as the real atoms can be treated as the virtual atoms for modeling, positioning VFN as a potential universal encoder. In protein diffusion (frame modeling), VFN exhibits an impressive performance advantage over IPA, excelling in terms of both designability (67.04% vs. 53.58%) and diversity (66.54% vs. 51.98%). In inverse folding (frame and atom modeling), VFN outperforms the previous SoTA model, PiFold (54.7% vs. 51.66%), on sequence recovery rate. We also propose a method of equipping VFN with the ESM model, which significantly surpasses the previous ESM-based SoTA (62.67% vs. 55.65%), LM-Design, by a substantial margin.

Large Language Model can reasonably understand and generate human expressions but may lack of thorough thinking and reasoning mechanisms. Recently there have been several studies which enhance the thinking ability of language models but most of them are not data-driven or training-based. In this paper, we are motivated by the cognitive mechanism in the natural world, and design a novel model architecture called TaS which allows it to first consider the thoughts and then express the response based upon the query. We design several pipelines to annotate or generate the thought contents from prompt-response samples, then add language heads in a middle layer which behaves as the thinking layer. We train the language model by the thoughts-augmented data and successfully let the thinking layer automatically generate reasonable thoughts and finally output more reasonable responses. Both qualitative examples and quantitative results validate the effectiveness and performance of TaS. Our code is available at https://anonymous.4open.science/r/TadE.

Antibody design is an essential yet challenging task in various domains like therapeutics and biology. There are two major defects in current learning-based methods: 1) tackling only a certain subtask of the whole antibody design pipeline, making them suboptimal or resource-intensive. 2) omitting either the framework regions or side chains, thus incapable of capturing the full-atom geometry. To address these pitfalls, we propose dynamic Multi-channel Equivariant grAph Network (dyMEAN), an end-to-end full-atom model for E(3)-equivariant antibody design given the epitope and the incomplete sequence of the antibody. Specifically, we first explore structural initialization as a knowledgeable guess of the antibody structure and then propose shadow paratope to bridge the epitope-antibody connections. Both 1D sequences and 3D structures are updated via an adaptive multi-channel equivariant encoder that is able to process protein residues of variable sizes when considering full atoms. Finally, the updated antibody is docked to the epitope via the alignment of the shadow paratope. Experiments on epitope-binding CDR-H3 design, complex structure prediction, and affinity optimization demonstrate the superiority of our end-to-end framework and full-atom modeling.

In this paper, we introduce the Tree-of-Thought (ToT) framework, a novel approach aimed at improving the problem-solving capabilities of auto-regressive large language models (LLMs). The ToT technique is inspired by the human mind's approach for solving complex reasoning tasks through trial and error. In this process, the human mind explores the solution space through a tree-like thought process, allowing for backtracking when necessary. To implement ToT as a software system, we augment an LLM with additional modules including a prompter agent, a checker module, a memory module, and a ToT controller. In order to solve a given problem, these modules engage in a multi-round conversation with the LLM. The memory module records the conversation and state history of the problem solving process, which allows the system to backtrack to the previous steps of the thought-process and explore other directions from there. To verify the effectiveness of the proposed technique, we implemented a ToT-based solver for the Sudoku Puzzle. Experimental results show that the ToT framework can significantly increase the success rate of Sudoku puzzle solving. Our implementation of the ToT-based Sudoku solver is available on GitHub: https://github.com/jieyilong/tree-of-thought-puzzle-solver.

Discovering novel high-entropy alloys (HEAs) with desirable properties is challenging due to the vast compositional space and complex phase formation mechanisms. Efficient exploration of this space requires a strategic approach that integrates heterogeneous knowledge sources. Here, we propose a framework that systematically combines knowledge extracted from computational material datasets with domain knowledge distilled from scientific literature using large language models (LLMs). A central feature of this approach is the explicit consideration of element substitutability, identifying chemically similar elements that can be interchanged to potentially stabilize desired HEAs. Dempster-Shafer theory, a mathematical framework for reasoning under uncertainty, is employed to model and combine substitutabilities based on aggregated evidence from multiple sources. The framework predicts the phase stability of candidate HEA compositions and is systematically evaluated on both quaternary alloy systems, demonstrating superior performance compared to baseline machine learning models and methods reliant on single-source evidence in cross-validation experiments. By leveraging multi-source knowledge, the framework retains robust predictive power even when key elements are absent from the training data, underscoring its potential for knowledge transfer and extrapolation. Furthermore, the enhanced interpretability of the methodology offers insights into the fundamental factors governing HEA formation. Overall, this work provides a promising strategy for accelerating HEA discovery by integrating computational and textual knowledge sources, enabling efficient exploration of vast compositional spaces with improved generalization and interpretability.

Foundation models applied to bio-molecular space hold promise to accelerate drug discovery. Molecular representation is key to building such models. Previous works have typically focused on a single representation or view of the molecules. Here, we develop a multi-view foundation model approach, that integrates molecular views of graph, image and text. Single-view foundation models are each pre-trained on a dataset of up to 200M molecules and then aggregated into combined representations. Our multi-view model is validated on a diverse set of 18 tasks, encompassing ligand-protein binding, molecular solubility, metabolism and toxicity. We show that the multi-view models perform robustly and are able to balance the strengths and weaknesses of specific views. We then apply this model to screen compounds against a large (>100 targets) set of G Protein-Coupled receptors (GPCRs). From this library of targets, we identify 33 that are related to Alzheimer's disease. On this subset, we employ our model to identify strong binders, which are validated through structure-based modeling and identification of key binding motifs.

Machine writing with large language models often relies on retrieval-augmented generation. However, these approaches remain confined within the boundaries of the model's predefined scope, limiting the generation of content with rich information. Specifically, vanilla-retrieved information tends to lack depth, utility, and suffers from redundancy, which negatively impacts the quality of generated articles, leading to shallow, repetitive, and unoriginal outputs. To address these issues, we propose OmniThink, a machine writing framework that emulates the human-like process of iterative expansion and reflection. The core idea behind OmniThink is to simulate the cognitive behavior of learners as they progressively deepen their knowledge of the topics. Experimental results demonstrate that OmniThink improves the knowledge density of generated articles without compromising metrics such as coherence and depth. Human evaluations and expert feedback further highlight the potential of OmniThink to address real-world challenges in the generation of long-form articles.

In the last few years, graph neural networks (GNNs) have become the standard toolkit for analyzing and learning from data on graphs. This emerging field has witnessed an extensive growth of promising techniques that have been applied with success to computer science, mathematics, biology, physics and chemistry. But for any successful field to become mainstream and reliable, benchmarks must be developed to quantify progress. This led us in March 2020 to release a benchmark framework that i) comprises of a diverse collection of mathematical and real-world graphs, ii) enables fair model comparison with the same parameter budget to identify key architectures, iii) has an open-source, easy-to-use and reproducible code infrastructure, and iv) is flexible for researchers to experiment with new theoretical ideas. As of December 2022, the GitHub repository has reached 2,000 stars and 380 forks, which demonstrates the utility of the proposed open-source framework through the wide usage by the GNN community. In this paper, we present an updated version of our benchmark with a concise presentation of the aforementioned framework characteristics, an additional medium-sized molecular dataset AQSOL, similar to the popular ZINC, but with a real-world measured chemical target, and discuss how this framework can be leveraged to explore new GNN designs and insights. As a proof of value of our benchmark, we study the case of graph positional encoding (PE) in GNNs, which was introduced with this benchmark and has since spurred interest of exploring more powerful PE for Transformers and GNNs in a robust experimental setting.

Molecular representation learning contributes to multiple downstream tasks such as molecular property prediction and drug design. To properly represent molecules, graph contrastive learning is a promising paradigm as it utilizes self-supervision signals and has no requirements for human annotations. However, prior works fail to incorporate fundamental domain knowledge into graph semantics and thus ignore the correlations between atoms that have common attributes but are not directly connected by bonds. To address these issues, we construct a Chemical Element Knowledge Graph (KG) to summarize microscopic associations between elements and propose a novel Knowledge-enhanced Contrastive Learning (KCL) framework for molecular representation learning. KCL framework consists of three modules. The first module, knowledge-guided graph augmentation, augments the original molecular graph based on the Chemical Element KG. The second module, knowledge-aware graph representation, extracts molecular representations with a common graph encoder for the original molecular graph and a Knowledge-aware Message Passing Neural Network (KMPNN) to encode complex information in the augmented molecular graph. The final module is a contrastive objective, where we maximize agreement between these two views of molecular graphs. Extensive experiments demonstrated that KCL obtained superior performances against state-of-the-art baselines on eight molecular datasets. Visualization experiments properly interpret what KCL has learned from atoms and attributes in the augmented molecular graphs. Our codes and data are available at https://github.com/ZJU-Fangyin/KCL.

Building generalist models has recently demonstrated remarkable capabilities in diverse scientific domains. Within the realm of molecular learning, several studies have explored unifying diverse tasks across diverse domains. However, negative conflicts and interference between molecules and knowledge from different domain may have a worse impact in threefold. First, conflicting molecular representations can lead to optimization difficulties for the models. Second, mixing and scaling up training data across diverse tasks is inherently challenging. Third, the computational cost of refined pretraining is prohibitively high. To address these limitations, this paper presents Omni-Mol, a scalable and unified LLM-based framework for direct instruction tuning. Omni-Mol builds on three key components to tackles conflicts: (1) a unified encoding mechanism for any task input; (2) an active-learning-driven data selection strategy that significantly reduces dataset size; (3) a novel design of the adaptive gradient stabilization module and anchor-and-reconcile MoE framework that ensures stable convergence. Experimentally, Omni-Mol achieves state-of-the-art performance across 15 molecular tasks, demonstrates the presence of scaling laws in the molecular domain, and is supported by extensive ablation studies and analyses validating the effectiveness of its design. The code and weights of the powerful AI-driven chemistry generalist are open-sourced at: https://anonymous.4open.science/r/Omni-Mol-8EDB.

Fragment-based drug discovery has been an effective paradigm in early-stage drug development. An open challenge in this area is designing linkers between disconnected molecular fragments of interest to obtain chemically-relevant candidate drug molecules. In this work, we propose DiffLinker, an E(3)-equivariant 3D-conditional diffusion model for molecular linker design. Given a set of disconnected fragments, our model places missing atoms in between and designs a molecule incorporating all the initial fragments. Unlike previous approaches that are only able to connect pairs of molecular fragments, our method can link an arbitrary number of fragments. Additionally, the model automatically determines the number of atoms in the linker and its attachment points to the input fragments. We demonstrate that DiffLinker outperforms other methods on the standard datasets generating more diverse and synthetically-accessible molecules. Besides, we experimentally test our method in real-world applications, showing that it can successfully generate valid linkers conditioned on target protein pockets.

We report a flexible multi-modal mechanics language model, MeLM, applied to solve various nonlinear forward and inverse problems, that can deal with a set of instructions, numbers and microstructure data. The framework is applied to various examples including bio-inspired hierarchical honeycomb design, carbon nanotube mechanics, and protein unfolding. In spite of the flexible nature of the model-which allows us to easily incorporate diverse materials, scales, and mechanical features-it performs well across disparate forward and inverse tasks. Based on an autoregressive attention-model, MeLM effectively represents a large multi-particle system consisting of hundreds of millions of neurons, where the interaction potentials are discovered through graph-forming self-attention mechanisms that are then used to identify relationships from emergent structures, while taking advantage of synergies discovered in the training data. We show that the model can solve complex degenerate mechanics design problems and determine novel material architectures across a range of hierarchical levels, providing an avenue for materials discovery and analysis. Looking beyond the demonstrations reported in this paper, we discuss other opportunities in applied mechanics and general considerations about the use of large language models in modeling, design, and analysis that can span a broad spectrum of material properties from mechanical, thermal, optical, to electronic.

Machine learning techniques are essential tools to compute efficient, yet accurate, force fields for atomistic simulations. This approach has recently been extended to incorporate quantum computational methods, making use of variational quantum learning models to predict potential energy surfaces and atomic forces from ab initio training data. However, the trainability and scalability of such models are still limited, due to both theoretical and practical barriers. Inspired by recent developments in geometric classical and quantum machine learning, here we design quantum neural networks that explicitly incorporate, as a data-inspired prior, an extensive set of physically relevant symmetries. We find that our invariant quantum learning models outperform their more generic counterparts on individual molecules of growing complexity. Furthermore, we study a water dimer as a minimal example of a system with multiple components, showcasing the versatility of our proposed approach and opening the way towards larger simulations. Our results suggest that molecular force fields generation can significantly profit from leveraging the framework of geometric quantum machine learning, and that chemical systems represent, in fact, an interesting and rich playground for the development and application of advanced quantum machine learning tools.

We propose an intuitive LLM prompting framework (AgentKit) for multifunctional agents. AgentKit offers a unified framework for explicitly constructing a complex "thought process" from simple natural language prompts. The basic building block in AgentKit is a node, containing a natural language prompt for a specific subtask. The user then puts together chains of nodes, like stacking LEGO pieces. The chains of nodes can be designed to explicitly enforce a naturally structured "thought process". For example, for the task of writing a paper, one may start with the thought process of 1) identify a core message, 2) identify prior research gaps, etc. The nodes in AgentKit can be designed and combined in different ways to implement multiple advanced capabilities including on-the-fly hierarchical planning, reflection, and learning from interactions. In addition, due to the modular nature and the intuitive design to simulate explicit human thought process, a basic agent could be implemented as simple as a list of prompts for the subtasks and therefore could be designed and tuned by someone without any programming experience. Quantitatively, we show that agents designed through AgentKit achieve SOTA performance on WebShop and Crafter. These advances underscore AgentKit's potential in making LLM agents effective and accessible for a wider range of applications. https://github.com/holmeswww/AgentKit

Chemical reasoning usually involves complex, multi-step processes that demand precise calculations, where even minor errors can lead to cascading failures. Furthermore, large language models (LLMs) encounter difficulties handling domain-specific formulas, executing reasoning steps accurately, and integrating code effectively when tackling chemical reasoning tasks. To address these challenges, we present ChemAgent, a novel framework designed to improve the performance of LLMs through a dynamic, self-updating library. This library is developed by decomposing chemical tasks into sub-tasks and compiling these sub-tasks into a structured collection that can be referenced for future queries. Then, when presented with a new problem, ChemAgent retrieves and refines pertinent information from the library, which we call memory, facilitating effective task decomposition and the generation of solutions. Our method designs three types of memory and a library-enhanced reasoning component, enabling LLMs to improve over time through experience. Experimental results on four chemical reasoning datasets from SciBench demonstrate that ChemAgent achieves performance gains of up to 46% (GPT-4), significantly outperforming existing methods. Our findings suggest substantial potential for future applications, including tasks such as drug discovery and materials science. Our code can be found at https://github.com/gersteinlab/chemagent

Large Reasoning Models (LRMs) represent a breakthrough in AI problem-solving capabilities, but their effectiveness in interactive environments can be limited. This paper introduces and analyzes overthinking in LRMs. A phenomenon where models favor extended internal reasoning chains over environmental interaction. Through experiments on software engineering tasks using SWE Bench Verified, we observe three recurring patterns: Analysis Paralysis, Rogue Actions, and Premature Disengagement. We propose a framework to study these behaviors, which correlates with human expert assessments, and analyze 4018 trajectories. We observe that higher overthinking scores correlate with decreased performance, with reasoning models exhibiting stronger tendencies toward overthinking compared to non-reasoning models. Our analysis reveals that simple efforts to mitigate overthinking in agentic environments, such as selecting the solution with the lower overthinking score, can improve model performance by almost 30% while reducing computational costs by 43%. These results suggest that mitigating overthinking has strong practical implications. We suggest that by leveraging native function-calling capabilities and selective reinforcement learning overthinking tendencies could be mitigated. We also open-source our evaluation framework and dataset to facilitate research in this direction at https://github.com/AlexCuadron/Overthinking.

We introduce Diagram of Thought (DoT), a framework that models iterative reasoning in large language models (LLMs) as the construction of a directed acyclic graph (DAG) within a single model. Unlike traditional approaches that represent reasoning as linear chains or trees, DoT organizes propositions, critiques, refinements, and verifications into a cohesive DAG structure, allowing the model to explore complex reasoning pathways while maintaining logical consistency. Each node in the diagram corresponds to a proposition that has been proposed, critiqued, refined, or verified, enabling the LLM to iteratively improve its reasoning through natural language feedback. By leveraging auto-regressive next-token prediction with role-specific tokens, DoT facilitates seamless transitions between proposing ideas and critically evaluating them, providing richer feedback than binary signals. Furthermore, we formalize the DoT framework using Topos Theory, providing a mathematical foundation that ensures logical consistency and soundness in the reasoning process. This approach enhances both the training and inference processes within a single LLM, eliminating the need for multiple models or external control mechanisms. DoT offers a conceptual framework for designing next-generation reasoning-specialized models, emphasizing training efficiency, robust reasoning capabilities, and theoretical grounding. The code is available at https://github.com/diagram-of-thought/diagram-of-thought.

We explore the integration of Kolmogorov Networks (KANs) into molecular dynamics (MD) simulations to improve interatomic potentials. We propose that widely used potentials, such as the Lennard-Jones (LJ) potential, the embedded atom model (EAM), and artificial neural network (ANN) potentials, can be interpreted within the KAN framework. Specifically, we demonstrate that the descriptors for ANN potentials, typically constructed using polynomials, can be redefined using KAN's non-linear functions. By employing linear or cubic spline interpolations for these KAN functions, we show that the computational cost of evaluating ANN potentials and their derivatives is reduced.

Deep generative models have recently achieved superior performance in 3D molecule generation. Most of them first generate atoms and then add chemical bonds based on the generated atoms in a post-processing manner. However, there might be no corresponding bond solution for the temporally generated atoms as their locations are generated without considering potential bonds. We define this problem as the atom-bond inconsistency problem and claim it is the main reason for current approaches to generating unrealistic 3D molecules. To overcome this problem, we propose a new diffusion model called MolDiff which can generate atoms and bonds simultaneously while still maintaining their consistency by explicitly modeling the dependence between their relationships. We evaluated the generation ability of our proposed model and the quality of the generated molecules using criteria related to both geometry and chemical properties. The empirical studies showed that our model outperforms previous approaches, achieving a three-fold improvement in success rate and generating molecules with significantly better quality.

Large language models' reasoning abilities benefit from methods that organize their thought processes, such as chain-of-thought prompting, which employs a sequential structure to guide the reasoning process step-by-step. However, existing approaches focus primarily on organizing the sequence of thoughts, leaving structure in individual thought steps underexplored. To address this gap, we propose Table as Thought, a framework inspired by cognitive neuroscience theories on human thought. Table as Thought organizes reasoning within a tabular schema, where rows represent sequential thought steps and columns capture critical constraints and contextual information to enhance reasoning. The reasoning process iteratively populates the table until self-verification ensures completeness and correctness. Our experiments show that Table as Thought excels in planning tasks and demonstrates a strong potential for enhancing LLM performance in mathematical reasoning compared to unstructured thought baselines. This work provides a novel exploration of refining thought representation within LLMs, paving the way for advancements in reasoning and AI cognition.

We present an agentic, autonomous graph expansion framework that iteratively structures and refines knowledge in situ. Unlike conventional knowledge graph construction methods relying on static extraction or single-pass learning, our approach couples a reasoning-native large language model with a continually updated graph representation. At each step, the system actively generates new concepts and relationships, merges them into a global graph, and formulates subsequent prompts based on its evolving structure. Through this feedback-driven loop, the model organizes information into a scale-free network characterized by hub formation, stable modularity, and bridging nodes that link disparate knowledge clusters. Over hundreds of iterations, new nodes and edges continue to appear without saturating, while centrality measures and shortest path distributions evolve to yield increasingly distributed connectivity. Our analysis reveals emergent patterns, such as the rise of highly connected 'hub' concepts and the shifting influence of 'bridge' nodes, indicating that agentic, self-reinforcing graph construction can yield open-ended, coherent knowledge structures. Applied to materials design problems, we present compositional reasoning experiments by extracting node-specific and synergy-level principles to foster genuinely novel knowledge synthesis, yielding cross-domain ideas that transcend rote summarization and strengthen the framework's potential for open-ended scientific discovery. We discuss other applications in scientific discovery and outline future directions for enhancing scalability and interpretability.

While Large Language Models (LLMs) have demonstrated enhanced capabilities in function-calling, these advancements primarily rely on accessing the functions' responses. This methodology is practical for simpler APIs but faces scalability issues with irreversible APIs that significantly impact the system, such as a database deletion API. Similarly, processes requiring extensive time for each API call and those necessitating forward planning, like automated action pipelines, present complex challenges. Furthermore, scenarios often arise where a generalized approach is needed because algorithms lack direct access to the specific implementations of these functions or secrets to use them. Traditional tool planning methods are inadequate in these cases, compelling the need to operate within black-box environments. Unlike their performance in tool manipulation, LLMs excel in black-box tasks, such as program synthesis. Therefore, we harness the program synthesis capabilities of LLMs to strategize tool usage in black-box settings, ensuring solutions are verified prior to implementation. We introduce TOPGUN, an ingeniously crafted approach leveraging program synthesis for black box tool planning. Accompanied by SwissNYF, a comprehensive suite that integrates black-box algorithms for planning and verification tasks, addressing the aforementioned challenges and enhancing the versatility and effectiveness of LLMs in complex API interactions. The public code for SwissNYF is available at https://github.com/iclr-dummy-user/SwissNYF.

Building a scalable and real-time recommendation system is vital for many businesses driven by time-sensitive customer feedback, such as short-videos ranking or online ads. Despite the ubiquitous adoption of production-scale deep learning frameworks like TensorFlow or PyTorch, these general-purpose frameworks fall short of business demands in recommendation scenarios for various reasons: on one hand, tweaking systems based on static parameters and dense computations for recommendation with dynamic and sparse features is detrimental to model quality; on the other hand, such frameworks are designed with batch-training stage and serving stage completely separated, preventing the model from interacting with customer feedback in real-time. These issues led us to reexamine traditional approaches and explore radically different design choices. In this paper, we present Monolith, a system tailored for online training. Our design has been driven by observations of our application workloads and production environment that reflects a marked departure from other recommendations systems. Our contributions are manifold: first, we crafted a collisionless embedding table with optimizations such as expirable embeddings and frequency filtering to reduce its memory footprint; second, we provide an production-ready online training architecture with high fault-tolerance; finally, we proved that system reliability could be traded-off for real-time learning. Monolith has successfully landed in the BytePlus Recommend product.

While there have been extensive studies in code generation by large language models (LLM), where benchmarks like HumanEval have been surpassed with an impressive 96.3% success rate, these benchmarks predominantly judge a model's performance on basic function-level code generation and lack the critical thinking and concept of scope required of real-world scenarios such as solving GitHub issues. This research introduces the application of the Tree of Thoughts (ToT) language model reasoning framework for enhancing the decision-making and problem-solving abilities of LLMs for this complex task. Compared to traditional input-output (IO) prompting and Retrieval Augmented Generation (RAG) techniques, ToT is designed to improve performance by facilitating a structured exploration of multiple reasoning trajectories and enabling self-assessment of potential solutions. We experimentally deploy ToT in tackling a Github issue contained within an instance of the SWE-bench. However, our results reveal that the ToT framework alone is not enough to give LLMs the critical reasoning capabilities to outperform existing methods. In this paper we analyze the potential causes of these shortcomings and identify key areas for improvement such as deepening the thought process and introducing agentic capabilities. The insights of this research are aimed at informing future directions for refining the application of ToT and better harnessing the potential of LLMs in real-world problem-solving scenarios.

A key challenge in artificial intelligence is the creation of systems capable of autonomously advancing scientific understanding by exploring novel domains, identifying complex patterns, and uncovering previously unseen connections in vast scientific data. In this work, we present SciAgents, an approach that leverages three core concepts: (1) the use of large-scale ontological knowledge graphs to organize and interconnect diverse scientific concepts, (2) a suite of large language models (LLMs) and data retrieval tools, and (3) multi-agent systems with in-situ learning capabilities. Applied to biologically inspired materials, SciAgents reveals hidden interdisciplinary relationships that were previously considered unrelated, achieving a scale, precision, and exploratory power that surpasses traditional human-driven research methods. The framework autonomously generates and refines research hypotheses, elucidating underlying mechanisms, design principles, and unexpected material properties. By integrating these capabilities in a modular fashion, the intelligent system yields material discoveries, critique and improve existing hypotheses, retrieve up-to-date data about existing research, and highlights their strengths and limitations. Our case studies demonstrate scalable capabilities to combine generative AI, ontological representations, and multi-agent modeling, harnessing a `swarm of intelligence' similar to biological systems. This provides new avenues for materials discovery and accelerates the development of advanced materials by unlocking Nature's design principles.

Entity resolution (record linkage, microclustering) systems are notoriously difficult to evaluate. Looking for a needle in a haystack, traditional evaluation methods use sophisticated, application-specific sampling schemes to find matching pairs of records among an immense number of non-matches. We propose an alternative that facilitates the creation of representative, reusable benchmark data sets without necessitating complex sampling schemes. These benchmark data sets can then be used for model training and a variety of evaluation tasks. Specifically, we propose an entity-centric data labeling methodology that integrates with a unified framework for monitoring summary statistics, estimating key performance metrics such as cluster and pairwise precision and recall, and analyzing root causes for errors. We validate the framework in an application to inventor name disambiguation and through simulation studies. Software: https://github.com/OlivierBinette/er-evaluation/

Property prediction accuracy has long been a key parameter of machine learning in materials informatics. Accordingly, advanced models showing state-of-the-art performance turn into highly parameterized black boxes missing interpretability. Here, we present an elegant way to make their reasoning transparent. Human-readable text-based descriptions automatically generated within a suite of open-source tools are proposed as materials representation. Transformer language models pretrained on 2 million peer-reviewed articles take as input well-known terms, e.g., chemical composition, crystal symmetry, and site geometry. Our approach outperforms crystal graph networks by classifying four out of five analyzed properties if one considers all available reference data. Moreover, fine-tuned text-based models show high accuracy in the ultra-small data limit. Explanations of their internal machinery are produced using local interpretability techniques and are faithful and consistent with domain expert rationales. This language-centric framework makes accurate property predictions accessible to people without artificial-intelligence expertise.

Predicting physical properties of materials from their crystal structures is a fundamental problem in materials science. In peripheral areas such as the prediction of molecular properties, fully connected attention networks have been shown to be successful. However, unlike these finite atom arrangements, crystal structures are infinitely repeating, periodic arrangements of atoms, whose fully connected attention results in infinitely connected attention. In this work, we show that this infinitely connected attention can lead to a computationally tractable formulation, interpreted as neural potential summation, that performs infinite interatomic potential summations in a deeply learned feature space. We then propose a simple yet effective Transformer-based encoder architecture for crystal structures called Crystalformer. Compared to an existing Transformer-based model, the proposed model requires only 29.4% of the number of parameters, with minimal modifications to the original Transformer architecture. Despite the architectural simplicity, the proposed method outperforms state-of-the-art methods for various property regression tasks on the Materials Project and JARVIS-DFT datasets.

The design of novel protein structures remains a challenge in protein engineering for applications across biomedicine and chemistry. In this line of work, a diffusion model over rigid bodies in 3D (referred to as frames) has shown success in generating novel, functional protein backbones that have not been observed in nature. However, there exists no principled methodological framework for diffusion on SE(3), the space of orientation preserving rigid motions in R3, that operates on frames and confers the group invariance. We address these shortcomings by developing theoretical foundations of SE(3) invariant diffusion models on multiple frames followed by a novel framework, FrameDiff, for learning the SE(3) equivariant score over multiple frames. We apply FrameDiff on monomer backbone generation and find it can generate designable monomers up to 500 amino acids without relying on a pretrained protein structure prediction network that has been integral to previous methods. We find our samples are capable of generalizing beyond any known protein structure.

Recently, pre-trained foundation models have enabled significant advancements in multiple fields. In molecular machine learning, however, where datasets are often hand-curated, and hence typically small, the lack of datasets with labeled features, and codebases to manage those datasets, has hindered the development of foundation models. In this work, we present seven novel datasets categorized by size into three distinct categories: ToyMix, LargeMix and UltraLarge. These datasets push the boundaries in both the scale and the diversity of supervised labels for molecular learning. They cover nearly 100 million molecules and over 3000 sparsely defined tasks, totaling more than 13 billion individual labels of both quantum and biological nature. In comparison, our datasets contain 300 times more data points than the widely used OGB-LSC PCQM4Mv2 dataset, and 13 times more than the quantum-only QM1B dataset. In addition, to support the development of foundational models based on our proposed datasets, we present the Graphium graph machine learning library which simplifies the process of building and training molecular machine learning models for multi-task and multi-level molecular datasets. Finally, we present a range of baseline results as a starting point of multi-task and multi-level training on these datasets. Empirically, we observe that performance on low-resource biological datasets show improvement by also training on large amounts of quantum data. This indicates that there may be potential in multi-task and multi-level training of a foundation model and fine-tuning it to resource-constrained downstream tasks.

Evaluation is the baton for the development of large language models. Current evaluations typically employ a single-item assessment paradigm for each atomic test objective, which struggles to discern whether a model genuinely possesses the required capabilities or merely memorizes/guesses the answers to specific questions. To this end, we propose a novel evaluation framework referred to as StructEval. Starting from an atomic test objective, StructEval deepens and broadens the evaluation by conducting a structured assessment across multiple cognitive levels and critical concepts, and therefore offers a comprehensive, robust and consistent evaluation for LLMs. Experiments on three widely-used benchmarks demonstrate that StructEval serves as a reliable tool for resisting the risk of data contamination and reducing the interference of potential biases, thereby providing more reliable and consistent conclusions regarding model capabilities. Our framework also sheds light on the design of future principled and trustworthy LLM evaluation protocols.

We propose fine-tuning large language models for generation of stable materials. While unorthodox, fine-tuning large language models on text-encoded atomistic data is simple to implement yet reliable, with around 90% of sampled structures obeying physical constraints on atom positions and charges. Using energy above hull calculations from both learned ML potentials and gold-standard DFT calculations, we show that our strongest model (fine-tuned LLaMA-2 70B) can generate materials predicted to be metastable at about twice the rate (49% vs 28%) of CDVAE, a competing diffusion model. Because of text prompting's inherent flexibility, our models can simultaneously be used for unconditional generation of stable material, infilling of partial structures and text-conditional generation. Finally, we show that language models' ability to capture key symmetries of crystal structures improves with model scale, suggesting that the biases of pretrained LLMs are surprisingly well-suited for atomistic data.

Foundation models have been transformational in machine learning fields such as natural language processing and computer vision. Similar success in atomic property prediction has been limited due to the challenges of training effective models across multiple chemical domains. To address this, we introduce Joint Multi-domain Pre-training (JMP), a supervised pre-training strategy that simultaneously trains on multiple datasets from different chemical domains, treating each dataset as a unique pre-training task within a multi-task framework. Our combined training dataset consists of sim120M systems from OC20, OC22, ANI-1x, and Transition-1x. We evaluate performance and generalization by fine-tuning over a diverse set of downstream tasks and datasets including: QM9, rMD17, MatBench, QMOF, SPICE, and MD22. JMP demonstrates an average improvement of 59% over training from scratch, and matches or sets state-of-the-art on 34 out of 40 tasks. Our work highlights the potential of pre-training strategies that utilize diverse data to advance property prediction across chemical domains, especially for low-data tasks.

Consistency and reliability are crucial for conducting AI research. Many famous research fields, such as object detection, have been compared and validated with solid benchmark frameworks. After AlphaFold2, the protein folding task has entered a new phase, and many methods are proposed based on the component of AlphaFold2. The importance of a unified research framework in protein folding contains implementations and benchmarks to consistently and fairly compare various approaches. To achieve this, we present Solvent, an protein folding framework that supports significant components of state-of-th-arts models in the manner of off-the-shelf interface Solvent contains different models implemented in a unified codebase and supports training and evaluation for defined models on the same dataset. We benchmark well-known algorithms and their components and provide experiments that give helpful insights into the protein structure modeling field. We hope that Solvent will increase the reliability and consistency of proposed models and gives efficiency in both speed and costs, resulting in acceleration on protein folding modeling research. The code is available at https://github.com/kakaobrain/solvent, and the project will continue to be developed.

Crystalline materials are a fundamental component in next-generation technologies, yet modeling their distribution presents unique computational challenges. Of the plausible arrangements of atoms in a periodic lattice only a vanishingly small percentage are thermodynamically stable, which is a key indicator of the materials that can be experimentally realized. Two fundamental tasks in this area are to (a) predict the stable crystal structure of a known composition of elements and (b) propose novel compositions along with their stable structures. We present FlowMM, a pair of generative models that achieve state-of-the-art performance on both tasks while being more efficient and more flexible than competing methods. We generalize Riemannian Flow Matching to suit the symmetries inherent to crystals: translation, rotation, permutation, and periodic boundary conditions. Our framework enables the freedom to choose the flow base distributions, drastically simplifying the problem of learning crystal structures compared with diffusion models. In addition to standard benchmarks, we validate FlowMM's generated structures with quantum chemistry calculations, demonstrating that it is about 3x more efficient, in terms of integration steps, at finding stable materials compared to previous open methods.

Large Language Models (LLMs) driven by In-Context Learning (ICL) have significantly improved the performance of text-to-SQL. Previous methods generally employ a two-stage reasoning framework, namely 1) schema linking and 2) logical synthesis, making the framework not only effective but also interpretable. Despite these advancements, the inherent bad nature of the generalization of LLMs often results in hallucinations, which limits the full potential of LLMs. In this work, we first identify and categorize the common types of hallucinations at each stage in text-to-SQL. We then introduce a novel strategy, Task Alignment (TA), designed to mitigate hallucinations at each stage. TA encourages LLMs to take advantage of experiences from similar tasks rather than starting the tasks from scratch. This can help LLMs reduce the burden of generalization, thereby mitigating hallucinations effectively. We further propose TA-SQL, a text-to-SQL framework based on this strategy. The experimental results and comprehensive analysis demonstrate the effectiveness and robustness of our framework. Specifically, it enhances the performance of the GPT-4 baseline by 21.23% relatively on BIRD dev and it yields significant improvements across six models and four mainstream, complex text-to-SQL benchmarks.

Modern large language models (LLMs) like ChatGPT have shown remarkable performance on general language tasks but still struggle on complex reasoning tasks, which drives the research on cognitive behaviors of LLMs to explore human-like problem-solving strategies. Along this direction, one representative strategy is self-reflection, which asks an LLM to refine the solution with the feedback generated by itself iteratively. However, our study shows that such reflection-style methods suffer from the Degeneration-of-Thought (DoT) problem: once the LLM has established confidence in its solutions, it is unable to generate novel thoughts later through reflection even if its initial stance is incorrect. To address the DoT problem, we propose a Multi-Agent Debate (MAD) framework, in which multiple agents express their arguments in the state of "tit for tat" and a judge manages the debate process to obtain a final solution. Clearly, our MAD framework encourages divergent thinking in LLMs which would be helpful for tasks that require deep levels of contemplation. Experiment results on two challenging datasets, commonsense machine translation and counter-intuitive arithmetic reasoning, demonstrate the effectiveness of our MAD framework. Extensive analyses suggest that the adaptive break of debate and the modest level of "tit for tat" state are required for MAD to obtain good performance. Moreover, we find that LLMs might not be a fair judge if different LLMs are used for agents. Codes: https://github.com/Skytliang/Multi-Agents-Debate

This paper challenges the recent paradigm in atomic property prediction that links progress to growing dataset sizes and computational resources. We show that pretraining on a carefully selected, task-relevant dataset can match or even surpass large-scale pretraining, while using as little as 1/24th of the computational cost. We introduce the Chemical Similarity Index (CSI), a novel metric inspired by computer vision's Fr\'echet Inception Distance, for molecular graphs which quantifies the alignment between upstream pretraining datasets and downstream tasks. By selecting the most relevant dataset with minimal CSI distance, we show that models pretrained on a smaller, focused dataset consistently outperform those pretrained on massive, mixed datasets such as JMP, even when those larger datasets include the relevant dataset. Counterintuitively, we also find that indiscriminately adding more data can degrade model performance when the additional data poorly aligns with the task at hand. Our findings highlight that quality often outperforms quantity in pretraining for atomic property prediction.

The ability to discover new materials with desirable properties is critical for numerous applications from helping mitigate climate change to advances in next generation computing hardware. AI has the potential to accelerate materials discovery and design by more effectively exploring the chemical space compared to other computational methods or by trial-and-error. While substantial progress has been made on AI for materials data, benchmarks, and models, a barrier that has emerged is the lack of publicly available training data and open pre-trained models. To address this, we present a Meta FAIR release of the Open Materials 2024 (OMat24) large-scale open dataset and an accompanying set of pre-trained models. OMat24 contains over 110 million density functional theory (DFT) calculations focused on structural and compositional diversity. Our EquiformerV2 models achieve state-of-the-art performance on the Matbench Discovery leaderboard and are capable of predicting ground-state stability and formation energies to an F1 score above 0.9 and an accuracy of 20 meV/atom, respectively. We explore the impact of model size, auxiliary denoising objectives, and fine-tuning on performance across a range of datasets including OMat24, MPtraj, and Alexandria. The open release of the OMat24 dataset and models enables the research community to build upon our efforts and drive further advancements in AI-assisted materials science.

Artificial Intelligence (AI) has made incredible progress recently. On the one hand, advanced foundation models like ChatGPT can offer powerful conversation, in-context learning and code generation abilities on a broad range of open-domain tasks. They can also generate high-level solution outlines for domain-specific tasks based on the common sense knowledge they have acquired. However, they still face difficulties with some specialized tasks because they lack enough domain-specific data during pre-training or they often have errors in their neural network computations on those tasks that need accurate executions. On the other hand, there are also many existing models and systems (symbolic-based or neural-based) that can do some domain-specific tasks very well. However, due to the different implementation or working mechanisms, they are not easily accessible or compatible with foundation models. Therefore, there is a clear and pressing need for a mechanism that can leverage foundation models to propose task solution outlines and then automatically match some of the sub-tasks in the outlines to the off-the-shelf models and systems with special functionalities to complete them. Inspired by this, we introduce TaskMatrix.AI as a new AI ecosystem that connects foundation models with millions of APIs for task completion. Unlike most previous work that aimed to improve a single AI model, TaskMatrix.AI focuses more on using existing foundation models (as a brain-like central system) and APIs of other AI models and systems (as sub-task solvers) to achieve diversified tasks in both digital and physical domains. As a position paper, we will present our vision of how to build such an ecosystem, explain each key component, and use study cases to illustrate both the feasibility of this vision and the main challenges we need to address next.

Can foundation models be guided to execute tasks involving legal reasoning? We believe that building a benchmark to answer this question will require sustained collaborative efforts between the computer science and legal communities. To that end, this short paper serves three purposes. First, we describe how IRAC-a framework legal scholars use to distinguish different types of legal reasoning-can guide the construction of a Foundation Model oriented benchmark. Second, we present a seed set of 44 tasks built according to this framework. We discuss initial findings, and highlight directions for new tasks. Finally-inspired by the Open Science movement-we make a call for the legal and computer science communities to join our efforts by contributing new tasks. This work is ongoing, and our progress can be tracked here: https://github.com/HazyResearch/legalbench.

Recent advancements in Large Language Models (LLMs) have revolutionized decision-making by breaking down complex problems into more manageable language sequences referred to as ``thoughts''. An effective thought design should consider three key perspectives: performance, efficiency, and flexibility. However, existing thought can at most exhibit two of these attributes. To address these limitations, we introduce a novel thought prompting approach called ``Everything of Thoughts'' (XoT) to defy the law of ``Penrose triangle of existing thought paradigms. XoT leverages pretrained reinforcement learning and Monte Carlo Tree Search (MCTS) to incorporate external domain knowledge into thoughts, thereby enhancing LLMs' capabilities and enabling them to generalize to unseen problems efficiently. Through the utilization of the MCTS-LLM collaborative thought revision framework, this approach autonomously produces high-quality comprehensive cognitive mappings with minimal LLM interactions. Additionally, XoT empowers LLMs to engage in unconstrained thinking, allowing for flexible cognitive mappings for problems with multiple solutions.

The development of efficient machine learning models for molecular systems representation is becoming crucial in scientific research. We introduce TensorNet, an innovative O(3)-equivariant message-passing neural network architecture that leverages Cartesian tensor representations. By using Cartesian tensor atomic embeddings, feature mixing is simplified through matrix product operations. Furthermore, the cost-effective decomposition of these tensors into rotation group irreducible representations allows for the separate processing of scalars, vectors, and tensors when necessary. Compared to higher-rank spherical tensor models, TensorNet demonstrates state-of-the-art performance with significantly fewer parameters. For small molecule potential energies, this can be achieved even with a single interaction layer. As a result of all these properties, the model's computational cost is substantially decreased. Moreover, the accurate prediction of vector and tensor molecular quantities on top of potential energies and forces is possible. In summary, TensorNet's framework opens up a new space for the design of state-of-the-art equivariant models.

Lattices are architected metamaterials whose properties strongly depend on their geometrical design. The analogy between lattices and graphs enables the use of graph neural networks (GNNs) as a faster surrogate model compared to traditional methods such as finite element modelling. In this work, we generate a big dataset of structure-property relationships for strut-based lattices. The dataset is made available to the community which can fuel the development of methods anchored in physical principles for the fitting of fourth-order tensors. In addition, we present a higher-order GNN model trained on this dataset. The key features of the model are (i) SE(3) equivariance, and (ii) consistency with the thermodynamic law of conservation of energy. We compare the model to non-equivariant models based on a number of error metrics and demonstrate its benefits in terms of predictive performance and reduced training requirements. Finally, we demonstrate an example application of the model to an architected material design task. The methods which we developed are applicable to fourth-order tensors beyond elasticity such as piezo-optical tensor etc.

While artificial intelligence has made remarkable strides in revealing the relationship between biological macromolecules' primary sequence and tertiary structure, designing RNA sequences based on specified tertiary structures remains challenging. Though existing approaches in protein design have thoroughly explored structure-to-sequence dependencies in proteins, RNA design still confronts difficulties due to structural complexity and data scarcity. Moreover, direct transplantation of protein design methodologies into RNA design fails to achieve satisfactory outcomes although sharing similar structural components. In this study, we aim to systematically construct a data-driven RNA design pipeline. We crafted a large, well-curated benchmark dataset and designed a comprehensive structural modeling approach to represent the complex RNA tertiary structure. More importantly, we proposed a hierarchical data-efficient representation learning framework that learns structural representations through contrastive learning at both cluster-level and sample-level to fully leverage the limited data. By constraining data representations within a limited hyperspherical space, the intrinsic relationships between data points could be explicitly imposed. Moreover, we incorporated extracted secondary structures with base pairs as prior knowledge to facilitate the RNA design process. Extensive experiments demonstrate the effectiveness of our proposed method, providing a reliable baseline for future RNA design tasks. The source code and benchmark dataset are available at https://github.com/A4Bio/RDesign.

Large Language Models (LLMs) have generated considerable interest and debate regarding their potential emergence of Theory of Mind (ToM). Several recent inquiries reveal a lack of robust ToM in these models and pose a pressing demand to develop new benchmarks, as current ones primarily focus on different aspects of ToM and are prone to shortcuts and data leakage. In this position paper, we seek to answer two road-blocking questions: (1) How can we taxonomize a holistic landscape of machine ToM? (2) What is a more effective evaluation protocol for machine ToM? Following psychological studies, we taxonomize machine ToM into 7 mental state categories and delineate existing benchmarks to identify under-explored aspects of ToM. We argue for a holistic and situated evaluation of ToM to break ToM into individual components and treat LLMs as an agent who is physically situated in environments and socially situated in interactions with humans. Such situated evaluation provides a more comprehensive assessment of mental states and potentially mitigates the risk of shortcuts and data leakage. We further present a pilot study in a grid world setup as a proof of concept. We hope this position paper can facilitate future research to integrate ToM with LLMs and offer an intuitive means for researchers to better position their work in the landscape of ToM. Project page: https://github.com/Mars-tin/awesome-theory-of-mind

We propose a new score-based approach to generate 3D molecules represented as atomic densities on regular grids. First, we train a denoising neural network that learns to map from a smooth distribution of noisy molecules to the distribution of real molecules. Then, we follow the neural empirical Bayes framework [Saremi and Hyvarinen, 2019] and generate molecules in two steps: (i) sample noisy density grids from a smooth distribution via underdamped Langevin Markov chain Monte Carlo, and (ii) recover the ``clean'' molecule by denoising the noisy grid with a single step. Our method, VoxMol, generates molecules in a fundamentally different way than the current state of the art (i.e., diffusion models applied to atom point clouds). It differs in terms of the data representation, the noise model, the network architecture and the generative modeling algorithm. VoxMol achieves comparable results to state of the art on unconditional 3D molecule generation while being simpler to train and faster to generate molecules.

Neural architectures that learn potential energy surfaces from molecular data have undergone fast improvement in recent years. A key driver of this success is the Message Passing Neural Network (MPNN) paradigm. Its favorable scaling with system size partly relies upon a spatial distance limit on messages. While this focus on locality is a useful inductive bias, it also impedes the learning of long-range interactions such as electrostatics and van der Waals forces. To address this drawback, we propose Ewald message passing: a nonlocal Fourier space scheme which limits interactions via a cutoff on frequency instead of distance, and is theoretically well-founded in the Ewald summation method. It can serve as an augmentation on top of existing MPNN architectures as it is computationally inexpensive and agnostic to architectural details. We test the approach with four baseline models and two datasets containing diverse periodic (OC20) and aperiodic structures (OE62). We observe robust improvements in energy mean absolute errors across all models and datasets, averaging 10% on OC20 and 16% on OE62. Our analysis shows an outsize impact of these improvements on structures with high long-range contributions to the ground truth energy.

A growing number of papers are published in the area of superconducting materials science. However, novel text and data mining (TDM) processes are still needed to efficiently access and exploit this accumulated knowledge, paving the way towards data-driven materials design. Herein, we present SuperMat (Superconductor Materials), an annotated corpus of linked data derived from scientific publications on superconductors, which comprises 142 articles, 16052 entities, and 1398 links that are characterised into six categories: the names, classes, and properties of materials; links to their respective superconducting critical temperature (Tc); and parametric conditions such as applied pressure or measurement methods. The construction of SuperMat resulted from a fruitful collaboration between computer scientists and material scientists, and its high quality is ensured through validation by domain experts. The quality of the annotation guidelines was ensured by satisfactory Inter Annotator Agreement (IAA) between the annotators and the domain experts. SuperMat includes the dataset, annotation guidelines, and annotation support tools that use automatic suggestions to help minimise human errors.

Achieving a balance between computational speed, prediction accuracy, and universal applicability in molecular simulations has been a persistent challenge. This paper presents substantial advancements in the TorchMD-Net software, a pivotal step forward in the shift from conventional force fields to neural network-based potentials. The evolution of TorchMD-Net into a more comprehensive and versatile framework is highlighted, incorporating cutting-edge architectures such as TensorNet. This transformation is achieved through a modular design approach, encouraging customized applications within the scientific community. The most notable enhancement is a significant improvement in computational efficiency, achieving a very remarkable acceleration in the computation of energy and forces for TensorNet models, with performance gains ranging from 2-fold to 10-fold over previous iterations. Other enhancements include highly optimized neighbor search algorithms that support periodic boundary conditions and the smooth integration with existing molecular dynamics frameworks. Additionally, the updated version introduces the capability to integrate physical priors, further enriching its application spectrum and utility in research. The software is available at https://github.com/torchmd/torchmd-net.

Smartphones have become indispensable in modern life, yet navigating complex tasks on mobile devices often remains frustrating. Recent advancements in large multimodal model (LMM)-based mobile agents have demonstrated the ability to perceive and act in mobile environments. However, current approaches face significant limitations: they fall short in addressing real-world human needs, struggle with reasoning-intensive and long-horizon tasks, and lack mechanisms to learn and improve from prior experiences. To overcome these challenges, we introduce Mobile-Agent-E, a hierarchical multi-agent framework capable of self-evolution through past experience. By hierarchical, we mean an explicit separation of high-level planning and low-level action execution. The framework comprises a Manager, responsible for devising overall plans by breaking down complex tasks into subgoals, and four subordinate agents--Perceptor, Operator, Action Reflector, and Notetaker--which handle fine-grained visual perception, immediate action execution, error verification, and information aggregation, respectively. Mobile-Agent-E also features a novel self-evolution module which maintains a persistent long-term memory comprising Tips and Shortcuts. Tips are general guidance and lessons learned from prior tasks on how to effectively interact with the environment. Shortcuts are reusable, executable sequences of atomic operations tailored for specific subroutines. The inclusion of Tips and Shortcuts facilitates continuous refinement in performance and efficiency. Alongside this framework, we introduce Mobile-Eval-E, a new benchmark featuring complex mobile tasks requiring long-horizon, multi-app interactions. Empirical results show that Mobile-Agent-E achieves a 22% absolute improvement over previous state-of-the-art approaches across three foundation model backbones. Project page: https://x-plug.github.io/MobileAgent.

The natural world is full of complex systems characterized by intricate relations between their components: from social interactions between individuals in a social network to electrostatic interactions between atoms in a protein. Topological Deep Learning (TDL) provides a comprehensive framework to process and extract knowledge from data associated with these systems, such as predicting the social community to which an individual belongs or predicting whether a protein can be a reasonable target for drug development. TDL has demonstrated theoretical and practical advantages that hold the promise of breaking ground in the applied sciences and beyond. However, the rapid growth of the TDL literature has also led to a lack of unification in notation and language across Topological Neural Network (TNN) architectures. This presents a real obstacle for building upon existing works and for deploying TNNs to new real-world problems. To address this issue, we provide an accessible introduction to TDL, and compare the recently published TNNs using a unified mathematical and graphical notation. Through an intuitive and critical review of the emerging field of TDL, we extract valuable insights into current challenges and exciting opportunities for future development.

Metal-organic frameworks (MOFs) are of immense interest in applications such as gas storage and carbon capture due to their exceptional porosity and tunable chemistry. Their modular nature has enabled the use of template-based methods to generate hypothetical MOFs by combining molecular building blocks in accordance with known network topologies. However, the ability of these methods to identify top-performing MOFs is often hindered by the limited diversity of the resulting chemical space. In this work, we propose MOFDiff: a coarse-grained (CG) diffusion model that generates CG MOF structures through a denoising diffusion process over the coordinates and identities of the building blocks. The all-atom MOF structure is then determined through a novel assembly algorithm. Equivariant graph neural networks are used for the diffusion model to respect the permutational and roto-translational symmetries. We comprehensively evaluate our model's capability to generate valid and novel MOF structures and its effectiveness in designing outstanding MOF materials for carbon capture applications with molecular simulations.

Foundation models are redefining how AI systems are built. Practitioners now follow a standard procedure to build their machine learning solutions: from a pre-trained foundation model, they fine-tune the weights on the target task of interest. So, the Internet is swarmed by a handful of foundation models fine-tuned on many diverse tasks: these individual fine-tunings exist in isolation without benefiting from each other. In our opinion, this is a missed opportunity, as these specialized models contain rich and diverse features. In this paper, we thus propose model ratatouille, a new strategy to recycle the multiple fine-tunings of the same foundation model on diverse auxiliary tasks. Specifically, we repurpose these auxiliary weights as initializations for multiple parallel fine-tunings on the target task; then, we average all fine-tuned weights to obtain the final model. This recycling strategy aims at maximizing the diversity in weights by leveraging the diversity in auxiliary tasks. Empirically, it improves the state of the art on the reference DomainBed benchmark for out-of-distribution generalization. Looking forward, this work contributes to the emerging paradigm of updatable machine learning where, akin to open-source software development, the community collaborates to reliably update machine learning models.

Recent advancements in biological research leverage the integration of molecules, proteins, and natural language to enhance drug discovery. However, current models exhibit several limitations, such as the generation of invalid molecular SMILES, underutilization of contextual information, and equal treatment of structured and unstructured knowledge. To address these issues, we propose BioT5, a comprehensive pre-training framework that enriches cross-modal integration in biology with chemical knowledge and natural language associations. BioT5 utilizes SELFIES for 100% robust molecular representations and extracts knowledge from the surrounding context of bio-entities in unstructured biological literature. Furthermore, BioT5 distinguishes between structured and unstructured knowledge, leading to more effective utilization of information. After fine-tuning, BioT5 shows superior performance across a wide range of tasks, demonstrating its strong capability of capturing underlying relations and properties of bio-entities. Our code is available at https://github.com/QizhiPei/BioT5{Github}.

Large Language Models have recently gained significant attention in scientific discovery for their extensive knowledge and advanced reasoning capabilities. However, they encounter challenges in effectively simulating observational feedback and grounding it with language to propel advancements in physical scientific discovery. Conversely, human scientists undertake scientific discovery by formulating hypotheses, conducting experiments, and revising theories through observational analysis. Inspired by this, we propose to enhance the knowledge-driven, abstract reasoning abilities of LLMs with the computational strength of simulations. We introduce Scientific Generative Agent (SGA), a bilevel optimization framework: LLMs act as knowledgeable and versatile thinkers, proposing scientific hypotheses and reason about discrete components, such as physics equations or molecule structures; meanwhile, simulations function as experimental platforms, providing observational feedback and optimizing via differentiability for continuous parts, such as physical parameters. We conduct extensive experiments to demonstrate our framework's efficacy in constitutive law discovery and molecular design, unveiling novel solutions that differ from conventional human expectations yet remain coherent upon analysis.

We report a series of deep learning models to solve complex forward and inverse design problems in molecular modeling and design. Using both diffusion models inspired by nonequilibrium thermodynamics and attention-based transformer architectures, we demonstrate a flexible framework to capture complex chemical structures. First trained on the QM9 dataset and a series of quantum mechanical properties (e.g. homo, lumo, free energy, heat capacity, etc.), we then generalize the model to study and design key properties of deep eutectic solvents. In addition to separate forward and inverse models, we also report an integrated fully prompt-based multi-task generative pretrained transformer model that solves multiple forward, inverse design, and prediction tasks, flexibly and within one model. We show that the multi-task generative model has the overall best performance and allows for flexible integration of multiple objectives, within one model, and for distinct chemistries, suggesting that synergies emerge during training of this large language model. Trained jointly in tasks related to the QM9 dataset and deep eutectic solvents (DESs), the model can predict various quantum mechanical properties and critical properties to achieve deep eutectic solvent behavior. Several novel combinations of DESs are proposed based on this framework.

Molecular representation is a foundational element in our understanding of the physical world. Its importance ranges from the fundamentals of chemical reactions to the design of new therapies and materials. Previous molecular machine learning models have employed strings, fingerprints, global features, and simple molecular graphs that are inherently information-sparse representations. However, as the complexity of prediction tasks increases, the molecular representation needs to encode higher fidelity information. This work introduces a novel approach to infusing quantum-chemical-rich information into molecular graphs via stereoelectronic effects. We show that the explicit addition of stereoelectronic interactions significantly improves the performance of molecular machine learning models. Furthermore, stereoelectronics-infused representations can be learned and deployed with a tailored double graph neural network workflow, enabling its application to any downstream molecular machine learning task. Finally, we show that the learned representations allow for facile stereoelectronic evaluation of previously intractable systems, such as entire proteins, opening new avenues of molecular design.

The efficient exploration of chemical space to design molecules with intended properties enables the accelerated discovery of drugs, materials, and catalysts, and is one of the most important outstanding challenges in chemistry. Encouraged by the recent surge in computer power and artificial intelligence development, many algorithms have been developed to tackle this problem. However, despite the emergence of many new approaches in recent years, comparatively little progress has been made in developing realistic benchmarks that reflect the complexity of molecular design for real-world applications. In this work, we develop a set of practical benchmark tasks relying on physical simulation of molecular systems mimicking real-life molecular design problems for materials, drugs, and chemical reactions. Additionally, we demonstrate the utility and ease of use of our new benchmark set by demonstrating how to compare the performance of several well-established families of algorithms. Surprisingly, we find that model performance can strongly depend on the benchmark domain. We believe that our benchmark suite will help move the field towards more realistic molecular design benchmarks, and move the development of inverse molecular design algorithms closer to designing molecules that solve existing problems in both academia and industry alike.

Large language models (LLMs) have been routinely used to solve various tasks using step-by-step reasoning. However, the structure of intermediate reasoning steps, or thoughts, is rigid and unidirectional, such as chains, trees, or acyclic-directed graphs. Consequently, the resulting inflexible and forward-only reasoning may not address challenging tasks and fail when the LLM frequently gives false responses, i.e., ``hallucinations''. This paper proposes a new reasoning framework, called Thought Rollback (TR), allowing LLMs to adaptively build thought structure while maintaining effective reasoning toward problem-solving under ``hallucinations''. The core mechanism of TR is rolling back thoughts, which allows LLMs to perform error analysis on thoughts, and thus roll back to any previously mistaken thought for revision. Subsequently, by including such trial-and-error in the prompt to guide the LLM, each rollback leads to one more reliable reasoning path. Therefore, starting with a simple prompt without human annotations, LLM with TR adaptively and gradually explores thoughts for a correct solution. Comprehensive experiments on mathematical problems and multi-task reasoning demonstrate the state-of-the-art performance of TR in terms of problem-solving rate and interaction cost. For instance, the solving rate of GPT-4 with TR outperforms the current best by 9% on the MATH dataset.

WebAssembly enables near-native execution in web applications and is increasingly adopted for tasks that demand high performance and robust security. However, its assembly-like syntax, implicit stack machine, and low-level data types make it extremely difficult for human developers to understand, spurring the need for effective WebAssembly reverse engineering techniques. In this paper, we propose StackSight, a novel neurosymbolic approach that combines Large Language Models (LLMs) with advanced program analysis to decompile complex WebAssembly code into readable C++ snippets. StackSight visualizes and tracks virtual stack alterations via a static analysis algorithm and then applies chain-of-thought prompting to harness LLM's complex reasoning capabilities. Evaluation results show that StackSight significantly improves WebAssembly decompilation. Our user study also demonstrates that code snippets generated by StackSight have significantly higher win rates and enable a better grasp of code semantics.

Accurate prediction of Drug-Target Affinity (DTA) is of vital importance in early-stage drug discovery, facilitating the identification of drugs that can effectively interact with specific targets and regulate their activities. While wet experiments remain the most reliable method, they are time-consuming and resource-intensive, resulting in limited data availability that poses challenges for deep learning approaches. Existing methods have primarily focused on developing techniques based on the available DTA data, without adequately addressing the data scarcity issue. To overcome this challenge, we present the SSM-DTA framework, which incorporates three simple yet highly effective strategies: (1) A multi-task training approach that combines DTA prediction with masked language modeling (MLM) using paired drug-target data. (2) A semi-supervised training method that leverages large-scale unpaired molecules and proteins to enhance drug and target representations. This approach differs from previous methods that only employed molecules or proteins in pre-training. (3) The integration of a lightweight cross-attention module to improve the interaction between drugs and targets, further enhancing prediction accuracy. Through extensive experiments on benchmark datasets such as BindingDB, DAVIS, and KIBA, we demonstrate the superior performance of our framework. Additionally, we conduct case studies on specific drug-target binding activities, virtual screening experiments, drug feature visualizations, and real-world applications, all of which showcase the significant potential of our work. In conclusion, our proposed SSM-DTA framework addresses the data limitation challenge in DTA prediction and yields promising results, paving the way for more efficient and accurate drug discovery processes. Our code is available at https://github.com/QizhiPei/SSM-DTA{Github}.

The integration of molecule and language has garnered increasing attention in molecular science. Recent advancements in Language Models (LMs) have demonstrated potential for the comprehensive modeling of molecule and language. However, existing works exhibit notable limitations. Most existing works overlook the modeling of 3D information, which is crucial for understanding molecular structures and also functions. While some attempts have been made to leverage external structure encoding modules to inject the 3D molecular information into LMs, there exist obvious difficulties that hinder the integration of molecular structure and language text, such as modality alignment and separate tuning. To bridge this gap, we propose 3D-MolT5, a unified framework designed to model both 1D molecular sequence and 3D molecular structure. The key innovation lies in our methodology for mapping fine-grained 3D substructure representations (based on 3D molecular fingerprints) to a specialized 3D token vocabulary for 3D-MolT5. This 3D structure token vocabulary enables the seamless combination of 1D sequence and 3D structure representations in a tokenized format, allowing 3D-MolT5 to encode molecular sequence (SELFIES), molecular structure, and text sequences within a unified architecture. Alongside, we further introduce 1D and 3D joint pre-training to enhance the model's comprehension of these diverse modalities in a joint representation space and better generalize to various tasks for our foundation model. Through instruction tuning on multiple downstream datasets, our proposed 3D-MolT5 shows superior performance than existing methods in molecular property prediction, molecule captioning, and text-based molecule generation tasks. Our code will be available on GitHub soon.

While knowledge distillation (transfer) has been attracting attentions from the research community, the recent development in the fields has heightened the need for reproducible studies and highly generalized frameworks to lower barriers to such high-quality, reproducible deep learning research. Several researchers voluntarily published frameworks used in their knowledge distillation studies to help other interested researchers reproduce their original work. Such frameworks, however, are usually neither well generalized nor maintained, thus researchers are still required to write a lot of code to refactor/build on the frameworks for introducing new methods, models, datasets and designing experiments. In this paper, we present our developed open-source framework built on PyTorch and dedicated for knowledge distillation studies. The framework is designed to enable users to design experiments by declarative PyYAML configuration files, and helps researchers complete the recently proposed ML Code Completeness Checklist. Using the developed framework, we demonstrate its various efficient training strategies, and implement a variety of knowledge distillation methods. We also reproduce some of their original experimental results on the ImageNet and COCO datasets presented at major machine learning conferences such as ICLR, NeurIPS, CVPR and ECCV, including recent state-of-the-art methods. All the source code, configurations, log files and trained model weights are publicly available at https://github.com/yoshitomo-matsubara/torchdistill .

Memory-augmented Large Language Models (LLMs) have demonstrated remarkable performance in long-term human-machine interactions, which basically relies on iterative recalling and reasoning of history to generate high-quality responses. However, such repeated recall-reason steps easily produce biased thoughts, i.e., inconsistent reasoning results when recalling the same history for different questions. On the contrary, humans can keep thoughts in the memory and recall them without repeated reasoning. Motivated by this human capability, we propose a novel memory mechanism called TiM (Think-in-Memory) that enables LLMs to maintain an evolved memory for storing historical thoughts along the conversation stream. The TiM framework consists of two crucial stages: (1) before generating a response, a LLM agent recalls relevant thoughts from memory, and (2) after generating a response, the LLM agent post-thinks and incorporates both historical and new thoughts to update the memory. Thus, TiM can eliminate the issue of repeated reasoning by saving the post-thinking thoughts as the history. Besides, we formulate the basic principles to organize the thoughts in memory based on the well-established operations, (i.e., insert, forget, and merge operations), allowing for dynamic updates and evolution of the thoughts. Furthermore, we introduce Locality-Sensitive Hashing into TiM to achieve efficient retrieval for the long-term conversations. We conduct qualitative and quantitative experiments on real-world and simulated dialogues covering a wide range of topics, demonstrating that equipping existing LLMs with TiM significantly enhances their performance in generating responses for long-term interactions.

Protein function prediction is a crucial task in bioinformatics, with significant implications for understanding biological processes and disease mechanisms. While the relationship between sequence and function has been extensively explored, translating protein structure to function continues to present substantial challenges. Various models, particularly, CNN and graph-based deep learning approaches that integrate structural and functional data, have been proposed to address these challenges. However, these methods often fall short in elucidating the functional significance of key residues essential for protein functionality, as they predominantly adopt a retrospective perspective, leading to suboptimal performance. Inspired by region proposal networks in computer vision, we introduce the Protein Region Proposal Network (ProteinRPN) for accurate protein function prediction. Specifically, the region proposal module component of ProteinRPN identifies potential functional regions (anchors) which are refined through the hierarchy-aware node drop pooling layer favoring nodes with defined secondary structures and spatial proximity. The representations of the predicted functional nodes are enriched using attention mechanisms and subsequently fed into a Graph Multiset Transformer, which is trained with supervised contrastive (SupCon) and InfoNCE losses on perturbed protein structures. Our model demonstrates significant improvements in predicting Gene Ontology (GO) terms, effectively localizing functional residues within protein structures. The proposed framework provides a robust, scalable solution for protein function annotation, advancing the understanding of protein structure-function relationships in computational biology.

Large Language Models (LLMs) have demonstrated remarkable potential in scientific domains, yet a fundamental question remains unanswered: Can we simulate human research communities with LLMs? Addressing this question can deepen our understanding of the processes behind idea brainstorming and inspire the automatic discovery of novel scientific insights. In this work, we propose ResearchTown, a multi-agent framework for research community simulation. Within this framework, the human research community is simplified and modeled as an agent-data graph, where researchers and papers are represented as agent-type and data-type nodes, respectively, and connected based on their collaboration relationships. We also introduce TextGNN, a text-based inference framework that models various research activities (e.g., paper reading, paper writing, and review writing) as special forms of a unified message-passing process on the agent-data graph. To evaluate the quality of the research simulation, we present ResearchBench, a benchmark that uses a node-masking prediction task for scalable and objective assessment based on similarity. Our experiments reveal three key findings: (1) ResearchTown can provide a realistic simulation of collaborative research activities, including paper writing and review writing; (2) ResearchTown can maintain robust simulation with multiple researchers and diverse papers; (3) ResearchTown can generate interdisciplinary research ideas that potentially inspire novel research directions.

Existing methods, such as concept bottleneck models (CBMs), have been successful in providing concept-based interpretations for black-box deep learning models. They typically work by predicting concepts given the input and then predicting the final class label given the predicted concepts. However, (1) they often fail to capture the high-order, nonlinear interaction between concepts, e.g., correcting a predicted concept (e.g., "yellow breast") does not help correct highly correlated concepts (e.g., "yellow belly"), leading to suboptimal final accuracy; (2) they cannot naturally quantify the complex conditional dependencies between different concepts and class labels (e.g., for an image with the class label "Kentucky Warbler" and a concept "black bill", what is the probability that the model correctly predicts another concept "black crown"), therefore failing to provide deeper insight into how a black-box model works. In response to these limitations, we propose Energy-based Concept Bottleneck Models (ECBMs). Our ECBMs use a set of neural networks to define the joint energy of candidate (input, concept, class) tuples. With such a unified interface, prediction, concept correction, and conditional dependency quantification are then represented as conditional probabilities, which are generated by composing different energy functions. Our ECBMs address both limitations of existing CBMs, providing higher accuracy and richer concept interpretations. Empirical results show that our approach outperforms the state-of-the-art on real-world datasets.

We introduce Multi-Objective Counterfactuals for Design (MCD), a novel method for counterfactual optimization in design problems. Counterfactuals are hypothetical situations that can lead to a different decision or choice. In this paper, the authors frame the counterfactual search problem as a design recommendation tool that can help identify modifications to a design, leading to better functional performance. MCD improves upon existing counterfactual search methods by supporting multi-objective queries, which are crucial in design problems, and by decoupling the counterfactual search and sampling processes, thus enhancing efficiency and facilitating objective tradeoff visualization. The paper demonstrates MCD's core functionality using a two-dimensional test case, followed by three case studies of bicycle design that showcase MCD's effectiveness in real-world design problems. In the first case study, MCD excels at recommending modifications to query designs that can significantly enhance functional performance, such as weight savings and improvements to the structural safety factor. The second case study demonstrates that MCD can work with a pre-trained language model to suggest design changes based on a subjective text prompt effectively. Lastly, the authors task MCD with increasing a query design's similarity to a target image and text prompt while simultaneously reducing weight and improving structural performance, demonstrating MCD's performance on a complex multimodal query. Overall, MCD has the potential to provide valuable recommendations for practitioners and design automation researchers looking for answers to their ``What if'' questions by exploring hypothetical design modifications and their impact on multiple design objectives. The code, test problems, and datasets used in the paper are available to the public at decode.mit.edu/projects/counterfactuals/.

Table-based reasoning with large language models (LLMs) is a promising direction to tackle many table understanding tasks, such as table-based question answering and fact verification. Compared with generic reasoning, table-based reasoning requires the extraction of underlying semantics from both free-form questions and semi-structured tabular data. Chain-of-Thought and its similar approaches incorporate the reasoning chain in the form of textual context, but it is still an open question how to effectively leverage tabular data in the reasoning chain. We propose the Chain-of-Table framework, where tabular data is explicitly used in the reasoning chain as a proxy for intermediate thoughts. Specifically, we guide LLMs using in-context learning to iteratively generate operations and update the table to represent a tabular reasoning chain. LLMs can therefore dynamically plan the next operation based on the results of the previous ones. This continuous evolution of the table forms a chain, showing the reasoning process for a given tabular problem. The chain carries structured information of the intermediate results, enabling more accurate and reliable predictions. Chain-of-Table achieves new state-of-the-art performance on WikiTQ, FeTaQA, and TabFact benchmarks across multiple LLM choices.

In engineering design, navigating complex decision-making landscapes demands a thorough exploration of the design, performance, and constraint spaces, often impeded by resource-intensive simulations. Data-driven methods can mitigate this challenge by harnessing historical data to delineate feasible domains, accelerate optimization, or evaluate designs. However, the implementation of these methods usually demands machine-learning expertise and multiple trials to choose the right method and hyperparameters. This makes them less accessible for numerous engineering situations. Additionally, there is an inherent trade-off between training speed and accuracy, with faster methods sometimes compromising precision. In our paper, we demonstrate that a recently released general-purpose transformer-based classification model, TabPFN, is both fast and accurate. Notably, it requires no dataset-specific training to assess new tabular data. TabPFN is a Prior-Data Fitted Network, which undergoes a one-time offline training across a broad spectrum of synthetic datasets and performs in-context learning. We evaluated TabPFN's efficacy across eight engineering design classification problems, contrasting it with seven other algorithms, including a state-of-the-art AutoML method. For these classification challenges, TabPFN consistently outperforms in speed and accuracy. It is also the most data-efficient and provides the added advantage of being differentiable and giving uncertainty estimates. Our findings advocate for the potential of pre-trained models that learn from synthetic data and require no domain-specific tuning to make data-driven engineering design accessible to a broader community and open ways to efficient general-purpose models valid across applications. Furthermore, we share a benchmark problem set for evaluating new classification algorithms in engineering design.

Large language models (LLMs) have demonstrated exceptional performance in planning the use of various functional tools, such as calculators and retrievers, particularly in question-answering tasks. In this paper, we expand the definition of these tools, centering on conceptual tools within the context of dialogue systems. A conceptual tool specifies a cognitive concept that aids systematic or investigative thought. These conceptual tools play important roles in practice, such as multiple psychological or tutoring strategies being dynamically applied in a single turn to compose helpful responses. To further enhance the reasoning and planning capability of LLMs with these conceptual tools, we introduce a multi-persona collaboration framework: Think-Plan-Execute (TPE). This framework decouples the response generation process into three distinct roles: Thinker, Planner, and Executor. Specifically, the Thinker analyzes the internal status exhibited in the dialogue context, such as user emotions and preferences, to formulate a global guideline. The Planner then generates executable plans to call different conceptual tools (e.g., sources or strategies), while the Executor compiles all intermediate results into a coherent response. This structured approach not only enhances the explainability and controllability of responses but also reduces token redundancy. We demonstrate the effectiveness of TPE across various dialogue response generation tasks, including multi-source (FoCus) and multi-strategy interactions (CIMA and PsyQA). This reveals its potential to handle real-world dialogue interactions that require more complicated tool learning beyond just functional tools. The full code and data will be released for reproduction.

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and the expanded availability of experimental 3D protein structures have accelerated structure prediction, the dynamic nature of protein structures has received limited attention. This study introduces an innovative 4D diffusion model incorporating molecular dynamics (MD) simulation data to learn dynamic protein structures. Our approach is distinguished by the following components: (1) a unified diffusion model capable of generating dynamic protein structures, including both the backbone and side chains, utilizing atomic grouping and side-chain dihedral angle predictions; (2) a reference network that enhances structural consistency by integrating the latent embeddings of the initial 3D protein structures; and (3) a motion alignment module aimed at improving temporal structural coherence across multiple time steps. To our knowledge, this is the first diffusion-based model aimed at predicting protein trajectories across multiple time steps simultaneously. Validation on benchmark datasets demonstrates that our model exhibits high accuracy in predicting dynamic 3D structures of proteins containing up to 256 amino acids over 32 time steps, effectively capturing both local flexibility in stable states and significant conformational changes.

Emerging large reasoning models (LRMs), such as DeepSeek-R1 models, leverage long chain-of-thought (CoT) reasoning to generate structured intermediate steps, enhancing their reasoning capabilities. However, long CoT does not inherently guarantee safe outputs, potentially leading to harmful consequences such as the introduction of security vulnerabilities in code or the spread of misinformation. Current research on large language model (LLM) safety usually focuses on short-answer responses, overlooking the long CoT style outputs of LRMs. To bridge this gap, we conduct a systematic study of LRM safety. First, we investigate safety evaluators calibrated against human annotations. Using our newly developed metrics, we thoroughly assess the safety of 12 state-of-the-art LRMs on StrongReject and WildJailbreak datasets. Our results show that LRMs are not safe compared to their reasoning advance. Further, we perform a fine-grained analysis of the reasoning trace and final answer. We find that three decoding strategies-ZeroThink, LessThink, and MoreThink-can improve model safety without additional training. However, these strategies either use constrained reasoning traces or incur high inference costs. To better strengthen LRM safety, we introduce SafeChain, the first-of-its-kind safety training dataset in CoT style. We fine-tune two LRMs with SafeChain, showing that it not only enhances model safety but also preserves performance across 6 reasoning benchmarks.

Accelerating material discovery holds the potential to greatly help mitigate the climate crisis. Discovering new solid-state materials such as electrocatalysts, super-ionic conductors or photovoltaic materials can have a crucial impact, for instance, in improving the efficiency of renewable energy production and storage. In this paper, we introduce Crystal-GFN, a generative model of crystal structures that sequentially samples structural properties of crystalline materials, namely the space group, composition and lattice parameters. This domain-inspired approach enables the flexible incorporation of physical and structural hard constraints, as well as the use of any available predictive model of a desired physicochemical property as an objective function. To design stable materials, one must target the candidates with the lowest formation energy. Here, we use as objective the formation energy per atom of a crystal structure predicted by a new proxy machine learning model trained on MatBench. The results demonstrate that Crystal-GFN is able to sample highly diverse crystals with low (median -3.1 eV/atom) predicted formation energy.

Foundation model development attracts a rapidly expanding body of contributors, scientists, and applications. To help shape responsible development practices, we introduce the Foundation Model Development Cheatsheet: a growing collection of 250+ tools and resources spanning text, vision, and speech modalities. We draw on a large body of prior work to survey resources (e.g. software, documentation, frameworks, guides, and practical tools) that support informed data selection, processing, and understanding, precise and limitation-aware artifact documentation, efficient model training, advance awareness of the environmental impact from training, careful model evaluation of capabilities, risks, and claims, as well as responsible model release, licensing and deployment practices. We hope this curated collection of resources helps guide more responsible development. The process of curating this list, enabled us to review the AI development ecosystem, revealing what tools are critically missing, misused, or over-used in existing practices. We find that (i) tools for data sourcing, model evaluation, and monitoring are critically under-serving ethical and real-world needs, (ii) evaluations for model safety, capabilities, and environmental impact all lack reproducibility and transparency, (iii) text and particularly English-centric analyses continue to dominate over multilingual and multi-modal analyses, and (iv) evaluation of systems, rather than just models, is needed so that capabilities and impact are assessed in context.

The development of reliable and extensible molecular mechanics (MM) force fields -- fast, empirical models characterizing the potential energy surface of molecular systems -- is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods. Trained in a single GPU-day to fit a large and diverse quantum chemical dataset of over 1.1M energy and force calculations, espaloma-0.3 reproduces quantum chemical energetic properties of chemical domains highly relevant to drug discovery, including small molecules, peptides, and nucleic acids. Moreover, this force field maintains the quantum chemical energy-minimized geometries of small molecules and preserves the condensed phase properties of peptides, self-consistently parametrizing proteins and ligands to produce stable simulations leading to highly accurate predictions of binding free energies. This methodology demonstrates significant promise as a path forward for systematically building more accurate force fields that are easily extensible to new chemical domains of interest.

Optimization of atomic structures presents a challenging problem, due to their highly rough and non-convex energy landscape, with wide applications in the fields of drug design, materials discovery, and mechanics. Here, we present a graph reinforcement learning approach, StriderNET, that learns a policy to displace the atoms towards low energy configurations. We evaluate the performance of StriderNET on three complex atomic systems, namely, binary Lennard-Jones particles, calcium silicate hydrates gel, and disordered silicon. We show that StriderNET outperforms all classical optimization algorithms and enables the discovery of a lower energy minimum. In addition, StriderNET exhibits a higher rate of reaching minima with energies, as confirmed by the average over multiple realizations. Finally, we show that StriderNET exhibits inductivity to unseen system sizes that are an order of magnitude different from the training system.

Deep learning has achieved impressive performance in many domains, such as computer vision and natural language processing, but its advantage over classical shallow methods on tabular datasets remains questionable. It is especially challenging to surpass the performance of tree-like ensembles, such as XGBoost or Random Forests, on small-sized datasets (less than 1k samples). To tackle this challenge, we introduce HyperTab, a hypernetwork-based approach to solving small sample problems on tabular datasets. By combining the advantages of Random Forests and neural networks, HyperTab generates an ensemble of neural networks, where each target model is specialized to process a specific lower-dimensional view of the data. Since each view plays the role of data augmentation, we virtually increase the number of training samples while keeping the number of trainable parameters unchanged, which prevents model overfitting. We evaluated HyperTab on more than 40 tabular datasets of a varying number of samples and domains of origin, and compared its performance with shallow and deep learning models representing the current state-of-the-art. We show that HyperTab consistently outranks other methods on small data (with a statistically significant difference) and scores comparable to them on larger datasets. We make a python package with the code available to download at https://pypi.org/project/hypertab/

Large language models (LLMs) have gained widespread interest due to their ability to process human language and perform tasks on which they have not been explicitly trained. This is relevant for the chemical sciences, which face the problem of small and diverse datasets that are frequently in the form of text. LLMs have shown promise in addressing these issues and are increasingly being harnessed to predict chemical properties, optimize reactions, and even design and conduct experiments autonomously. However, we still have only a very limited systematic understanding of the chemical reasoning capabilities of LLMs, which would be required to improve models and mitigate potential harms. Here, we introduce "ChemBench," an automated framework designed to rigorously evaluate the chemical knowledge and reasoning abilities of state-of-the-art LLMs against the expertise of human chemists. We curated more than 7,000 question-answer pairs for a wide array of subfields of the chemical sciences, evaluated leading open and closed-source LLMs, and found that the best models outperformed the best human chemists in our study on average. The models, however, struggle with some chemical reasoning tasks that are easy for human experts and provide overconfident, misleading predictions, such as about chemicals' safety profiles. These findings underscore the dual reality that, although LLMs demonstrate remarkable proficiency in chemical tasks, further research is critical to enhancing their safety and utility in chemical sciences. Our findings also indicate a need for adaptations to chemistry curricula and highlight the importance of continuing to develop evaluation frameworks to improve safe and useful LLMs.

The automatic analysis of chemical literature has immense potential to accelerate the discovery of new materials and drugs. Much of the critical information in patent documents and scientific articles is contained in figures, depicting the molecule structures. However, automatically parsing the exact chemical structure is a formidable challenge, due to the amount of detailed information, the diversity of drawing styles, and the need for training data. In this work, we introduce MolGrapher to recognize chemical structures visually. First, a deep keypoint detector detects the atoms. Second, we treat all candidate atoms and bonds as nodes and put them in a graph. This construct allows a natural graph representation of the molecule. Last, we classify atom and bond nodes in the graph with a Graph Neural Network. To address the lack of real training data, we propose a synthetic data generation pipeline producing diverse and realistic results. In addition, we introduce a large-scale benchmark of annotated real molecule images, USPTO-30K, to spur research on this critical topic. Extensive experiments on five datasets show that our approach significantly outperforms classical and learning-based methods in most settings. Code, models, and datasets are available.

Matbench Discovery simulates the deployment of machine learning (ML) energy models in a high-throughput search for stable inorganic crystals. We address the disconnect between (i) thermodynamic stability and formation energy and (ii) in-domain vs out-of-distribution performance. Alongside this paper, we publish a Python package to aid with future model submissions and a growing online leaderboard with further insights into trade-offs between various performance metrics. To answer the question which ML methodology performs best at materials discovery, our initial release explores a variety of models including random forests, graph neural networks (GNN), one-shot predictors, iterative Bayesian optimizers and universal interatomic potentials (UIP). Ranked best-to-worst by their test set F1 score on thermodynamic stability prediction, we find CHGNet > M3GNet > MACE > ALIGNN > MEGNet > CGCNN > CGCNN+P > Wrenformer > BOWSR > Voronoi tessellation fingerprints with random forest. The top 3 models are UIPs, the winning methodology for ML-guided materials discovery, achieving F1 scores of ~0.6 for crystal stability classification and discovery acceleration factors (DAF) of up to 5x on the first 10k most stable predictions compared to dummy selection from our test set. We also highlight a sharp disconnect between commonly used global regression metrics and more task-relevant classification metrics. Accurate regressors are susceptible to unexpectedly high false-positive rates if those accurate predictions lie close to the decision boundary at 0 eV/atom above the convex hull where most materials are. Our results highlight the need to focus on classification metrics that actually correlate with improved stability hit rate.

Generating the periodic structure of stable materials is a long-standing challenge for the material design community. This task is difficult because stable materials only exist in a low-dimensional subspace of all possible periodic arrangements of atoms: 1) the coordinates must lie in the local energy minimum defined by quantum mechanics, and 2) global stability also requires the structure to follow the complex, yet specific bonding preferences between different atom types. Existing methods fail to incorporate these factors and often lack proper invariances. We propose a Crystal Diffusion Variational Autoencoder (CDVAE) that captures the physical inductive bias of material stability. By learning from the data distribution of stable materials, the decoder generates materials in a diffusion process that moves atomic coordinates towards a lower energy state and updates atom types to satisfy bonding preferences between neighbors. Our model also explicitly encodes interactions across periodic boundaries and respects permutation, translation, rotation, and periodic invariances. We significantly outperform past methods in three tasks: 1) reconstructing the input structure, 2) generating valid, diverse, and realistic materials, and 3) generating materials that optimize a specific property. We also provide several standard datasets and evaluation metrics for the broader machine learning community.

Artificial intelligence is transforming computational materials science, improving the prediction of material properties, and accelerating the discovery of novel materials. Recently, publicly available material data repositories have grown rapidly. This growth encompasses not only more materials, but also a greater variety and quantity of their associated properties. Existing machine learning efforts in materials science focus primarily on single-modality tasks, i.e., relationships between materials and a single physical property, thus not taking advantage of the rich and multimodal set of material properties. Here, we introduce Multimodal Learning for Materials (MultiMat), which enables self-supervised multi-modality training of foundation models for materials. We demonstrate our framework's potential using data from the Materials Project database on multiple axes: (i) MultiMat achieves state-of-the-art performance for challenging material property prediction tasks; (ii) MultiMat enables novel and accurate material discovery via latent space similarity, enabling screening for stable materials with desired properties; and (iii) MultiMat encodes interpretable emergent features that may provide novel scientific insights.

This paper presents a powerful framework to customize video creations by incorporating multiple specific identity (ID) photos, with video diffusion Transformers, referred to as Ingredients. Generally, our method consists of three primary modules: (i) a facial extractor that captures versatile and precise facial features for each human ID from both global and local perspectives; (ii) a multi-scale projector that maps face embeddings into the contextual space of image query in video diffusion transformers; (iii) an ID router that dynamically combines and allocates multiple ID embedding to the corresponding space-time regions. Leveraging a meticulously curated text-video dataset and a multi-stage training protocol, Ingredients demonstrates superior performance in turning custom photos into dynamic and personalized video content. Qualitative evaluations highlight the advantages of proposed method, positioning it as a significant advancement toward more effective generative video control tools in Transformer-based architecture, compared to existing methods. The data, code, and model weights are publicly available at: https://github.com/feizc/Ingredients.

Large language models demonstrate remarkable capabilities across various domains, especially mathematics and logic reasoning. However, current evaluations overlook physics-based reasoning - a complex task requiring physics theorems and constraints. We present PhysReason, a 1,200-problem benchmark comprising knowledge-based (25%) and reasoning-based (75%) problems, where the latter are divided into three difficulty levels (easy, medium, hard). Notably, problems require an average of 8.1 solution steps, with hard requiring 15.6, reflecting the complexity of physics-based reasoning. We propose the Physics Solution Auto Scoring Framework, incorporating efficient answer-level and comprehensive step-level evaluations. Top-performing models like Deepseek-R1, Gemini-2.0-Flash-Thinking, and o3-mini-high achieve less than 60% on answer-level evaluation, with performance dropping from knowledge questions (75.11%) to hard problems (31.95%). Through step-level evaluation, we identified four key bottlenecks: Physics Theorem Application, Physics Process Understanding, Calculation, and Physics Condition Analysis. These findings position PhysReason as a novel and comprehensive benchmark for evaluating physics-based reasoning capabilities in large language models. Our code and data will be published at https:/dxzxy12138.github.io/PhysReason.

Researchers are investing substantial effort in developing powerful general-purpose agents, wherein Foundation Models are used as modules within agentic systems (e.g. Chain-of-Thought, Self-Reflection, Toolformer). However, the history of machine learning teaches us that hand-designed solutions are eventually replaced by learned solutions. We formulate a new research area, Automated Design of Agentic Systems (ADAS), which aims to automatically create powerful agentic system designs, including inventing novel building blocks and/or combining them in new ways. We further demonstrate that there is an unexplored yet promising approach within ADAS where agents can be defined in code and new agents can be automatically discovered by a meta agent programming ever better ones in code. Given that programming languages are Turing Complete, this approach theoretically enables the learning of any possible agentic system: including novel prompts, tool use, control flows, and combinations thereof. We present a simple yet effective algorithm named Meta Agent Search to demonstrate this idea, where a meta agent iteratively programs interesting new agents based on an ever-growing archive of previous discoveries. Through extensive experiments across multiple domains including coding, science, and math, we show that our algorithm can progressively invent agents with novel designs that greatly outperform state-of-the-art hand-designed agents. Importantly, we consistently observe the surprising result that agents invented by Meta Agent Search maintain superior performance even when transferred across domains and models, demonstrating their robustness and generality. Provided we develop it safely, our work illustrates the potential of an exciting new research direction toward automatically designing ever-more powerful agentic systems to benefit humanity.

We explore how iterative revising a chain of thoughts with the help of information retrieval significantly improves large language models' reasoning and generation ability in long-horizon generation tasks, while hugely mitigating hallucination. In particular, the proposed method -- *retrieval-augmented thoughts* (RAT) -- revises each thought step one by one with retrieved information relevant to the task query, the current and the past thought steps, after the initial zero-shot CoT is generated. Applying RAT to GPT-3.5, GPT-4, and CodeLLaMA-7b substantially improves their performances on various long-horizon generation tasks; on average of relatively increasing rating scores by 13.63% on code generation, 16.96% on mathematical reasoning, 19.2% on creative writing, and 42.78% on embodied task planning. The demo page can be found at https://craftjarvis.github.io/RAT

There is increasing adoption of artificial intelligence in drug discovery. However, existing studies use machine learning to mainly utilize the chemical structures of molecules but ignore the vast textual knowledge available in chemistry. Incorporating textual knowledge enables us to realize new drug design objectives, adapt to text-based instructions and predict complex biological activities. Here we present a multi-modal molecule structure-text model, MoleculeSTM, by jointly learning molecules' chemical structures and textual descriptions via a contrastive learning strategy. To train MoleculeSTM, we construct a large multi-modal dataset, namely, PubChemSTM, with over 280,000 chemical structure-text pairs. To demonstrate the effectiveness and utility of MoleculeSTM, we design two challenging zero-shot tasks based on text instructions, including structure-text retrieval and molecule editing. MoleculeSTM has two main properties: open vocabulary and compositionality via natural language. In experiments, MoleculeSTM obtains the state-of-the-art generalization ability to novel biochemical concepts across various benchmarks.

Retrieval models aim at selecting a small set of item candidates which match the preference of a given user. They play a vital role in large-scale recommender systems since subsequent models such as rankers highly depend on the quality of item candidates. However, most existing retrieval models employ a single-round inference paradigm, which may not adequately capture the dynamic nature of user preferences and stuck in one area in the item space. In this paper, we propose Ada-Retrieval, an adaptive multi-round retrieval paradigm for recommender systems that iteratively refines user representations to better capture potential candidates in the full item space. Ada-Retrieval comprises two key modules: the item representation adapter and the user representation adapter, designed to inject context information into items' and users' representations. The framework maintains a model-agnostic design, allowing seamless integration with various backbone models such as RNNs or Transformers. We perform experiments on three widely used public datasets, incorporating five powerful sequential recommenders as backbone models. Our results demonstrate that Ada-Retrieval significantly enhances the performance of various base models, with consistent improvements observed across different datasets. Our code and data are publicly available at: https://github.com/ll0ruc/Ada-Retrieval.

Recent advancements in Chain-of-Thoughts (CoT) and Program-of-Thoughts (PoT) methods have greatly enhanced language models' mathematical reasoning capabilities, facilitating their integration into instruction tuning datasets with LLMs. However, existing methods for large-scale dataset creation require substantial seed data and high computational costs for data synthesis, posing significant challenges for scalability. We introduce InfinityMATH, a scalable instruction tuning dataset for programmatic mathematical reasoning. The construction pipeline emphasizes decoupling numbers from mathematical problems to synthesize number-independent programs, enabling efficient and flexible scaling while minimizing dependency on specific numerical values. Fine-tuning experiments with open-source language and code models, such as Llama2 and CodeLlama, demonstrate the practical benefits of InfinityMATH. These fine-tuned models, showed significant relative improvements on both in-domain and out-of-domain benchmarks, ranging from 184.7% to 514.3% on average. Additionally, these models exhibited high robustness on the GSM8K+ and MATH+ benchmarks, which are enhanced version of test sets with simply the number variations. InfinityMATH ensures that models are more versatile and effective across a broader range of mathematical problems. The data is available at https://huggingface.co/datasets/flagopen/InfinityMATH.

The rapid development of AI systems has been greatly influenced by the emergence of foundation models. A common approach for targeted problems involves fine-tuning these pre-trained foundation models for specific target tasks, resulting in a rapid spread of models fine-tuned across a diverse array of tasks. This work focuses on the problem of merging multiple fine-tunings of the same foundation model derived from a spectrum of auxiliary tasks. We introduce a new simple method, Model Breadcrumbs, which consists of a sparsely defined set of weights that carve out a trajectory within the weight space of a pre-trained model, enhancing task performance when traversed. These breadcrumbs are constructed by subtracting the weights from a pre-trained model before and after fine-tuning, followed by a sparsification process that eliminates weight outliers and negligible perturbations. Our experiments demonstrate the effectiveness of Model Breadcrumbs to simultaneously improve performance across multiple tasks. This contribution aligns with the evolving paradigm of updatable machine learning, reminiscent of the collaborative principles underlying open-source software development, fostering a community-driven effort to reliably update machine learning models. Our method is shown to be more efficient and unlike previous proposals does not require hyperparameter tuning for each new task added. Through extensive experimentation involving various models, tasks, and modalities we establish that integrating Model Breadcrumbs offers a simple, efficient, and highly effective approach for constructing multi-task models and facilitating updates to foundation models.

Recent advancements in artificial intelligence have sparked interest in scientific assistants that could support researchers across the full spectrum of scientific workflows, from literature review to experimental design and data analysis. A key capability for such systems is the ability to process and reason about scientific information in both visual and textual forms - from interpreting spectroscopic data to understanding laboratory setups. Here, we introduce MaCBench, a comprehensive benchmark for evaluating how vision-language models handle real-world chemistry and materials science tasks across three core aspects: data extraction, experimental understanding, and results interpretation. Through a systematic evaluation of leading models, we find that while these systems show promising capabilities in basic perception tasks - achieving near-perfect performance in equipment identification and standardized data extraction - they exhibit fundamental limitations in spatial reasoning, cross-modal information synthesis, and multi-step logical inference. Our insights have important implications beyond chemistry and materials science, suggesting that developing reliable multimodal AI scientific assistants may require advances in curating suitable training data and approaches to training those models.

We present Spacerini, a modular framework for seamless building and deployment of interactive search applications, designed to facilitate the qualitative analysis of large scale research datasets. Spacerini integrates features from both the Pyserini toolkit and the Hugging Face ecosystem to ease the indexing text collections and deploy them as search engines for ad-hoc exploration and to make the retrieval of relevant data points quick and efficient. The user-friendly interface enables searching through massive datasets in a no-code fashion, making Spacerini broadly accessible to anyone looking to qualitatively audit their text collections. This is useful both to IR~researchers aiming to demonstrate the capabilities of their indexes in a simple and interactive way, and to NLP~researchers looking to better understand and audit the failure modes of large language models. The framework is open source and available on GitHub: https://github.com/castorini/hf-spacerini, and includes utilities to load, pre-process, index, and deploy local and web search applications. A portfolio of applications created with Spacerini for a multitude of use cases can be found by visiting https://hf.co/spacerini.

While large language models (LLMs) have demonstrated impressive capabilities across tasks in language understanding and interactive decision making, their abilities for reasoning (e.g. chain-of-thought prompting) and acting (e.g. action plan generation) have primarily been studied as separate topics. In this paper, we explore the use of LLMs to generate both reasoning traces and task-specific actions in an interleaved manner, allowing for greater synergy between the two: reasoning traces help the model induce, track, and update action plans as well as handle exceptions, while actions allow it to interface with external sources, such as knowledge bases or environments, to gather additional information. We apply our approach, named ReAct, to a diverse set of language and decision making tasks and demonstrate its effectiveness over state-of-the-art baselines, as well as improved human interpretability and trustworthiness over methods without reasoning or acting components. Concretely, on question answering (HotpotQA) and fact verification (Fever), ReAct overcomes issues of hallucination and error propagation prevalent in chain-of-thought reasoning by interacting with a simple Wikipedia API, and generates human-like task-solving trajectories that are more interpretable than baselines without reasoning traces. On two interactive decision making benchmarks (ALFWorld and WebShop), ReAct outperforms imitation and reinforcement learning methods by an absolute success rate of 34% and 10% respectively, while being prompted with only one or two in-context examples. Project site with code: https://react-lm.github.io

While machine learning on graphs has demonstrated promise in drug design and molecular property prediction, significant benchmarking challenges hinder its further progress and relevance. Current benchmarking practices often lack focus on transformative, real-world applications, favoring narrow domains like two-dimensional molecular graphs over broader, impactful areas such as combinatorial optimization, relational databases, or chip design. Additionally, many benchmark datasets poorly represent the underlying data, leading to inadequate abstractions and misaligned use cases. Fragmented evaluations and an excessive focus on accuracy further exacerbate these issues, incentivizing overfitting rather than fostering generalizable insights. These limitations have prevented the development of truly useful graph foundation models. This position paper calls for a paradigm shift toward more meaningful benchmarks, rigorous evaluation protocols, and stronger collaboration with domain experts to drive impactful and reliable advances in graph learning research, unlocking the potential of graph learning.

We present MOFA, an open-source generative AI (GenAI) plus simulation workflow for high-throughput generation of metal-organic frameworks (MOFs) on large-scale high-performance computing (HPC) systems. MOFA addresses key challenges in integrating GPU-accelerated computing for GPU-intensive GenAI tasks, including distributed training and inference, alongside CPU- and GPU-optimized tasks for screening and filtering AI-generated MOFs using molecular dynamics, density functional theory, and Monte Carlo simulations. These heterogeneous tasks are unified within an online learning framework that optimizes the utilization of available CPU and GPU resources across HPC systems. Performance metrics from a 450-node (14,400 AMD Zen 3 CPUs + 1800 NVIDIA A100 GPUs) supercomputer run demonstrate that MOFA achieves high-throughput generation of novel MOF structures, with CO_2 adsorption capacities ranking among the top 10 in the hypothetical MOF (hMOF) dataset. Furthermore, the production of high-quality MOFs exhibits a linear relationship with the number of nodes utilized. The modular architecture of MOFA will facilitate its integration into other scientific applications that dynamically combine GenAI with large-scale simulations.

While chain-of-thought (CoT) prompting has revolutionized how LLMs perform reasoning tasks, its current methods and variations (e.g, Self-consistency, ReACT, Reflexion, Tree-of-Thoughts (ToT), Cumulative Reasoning (CR)) suffer from limitations like slowness, limited context grounding, hallucination and inconsistent outputs. To overcome these challenges, we introduce Evidence to Generate (E2G), a novel single-agent, two-step prompting framework. Instead of unverified reasoning claims, this innovative approach leverages the power of "evidence for decision making" by first focusing exclusively on the thought sequences (the series of intermediate steps) explicitly mentioned in the context which then serve as extracted evidence, guiding the LLM's output generation process with greater precision and efficiency. This simple yet powerful approach unlocks the true potential of chain-of-thought like prompting, paving the way for faster, more reliable, and more contextually aware reasoning in LLMs. \tool achieves remarkable results robustly across a wide range of knowledge-intensive reasoning and generation tasks, surpassing baseline approaches with state-of-the-art LLMs. For example, (i) on LogiQA benchmark using GPT-4 as backbone model, \tool achieves a new state-of-the Accuracy of 53.8% exceeding CoT by 18%, ToT by 11%, CR by 9% (ii) a variant of E2G with PaLM2 outperforms the variable-shot performance of Gemini Ultra by 0.9 F1 points, reaching an F1 score of 83.3 on a subset of DROP.

Catalyst discovery and optimization is key to solving many societal and energy challenges including solar fuels synthesis, long-term energy storage, and renewable fertilizer production. Despite considerable effort by the catalysis community to apply machine learning models to the computational catalyst discovery process, it remains an open challenge to build models that can generalize across both elemental compositions of surfaces and adsorbate identity/configurations, perhaps because datasets have been smaller in catalysis than related fields. To address this we developed the OC20 dataset, consisting of 1,281,040 Density Functional Theory (DFT) relaxations (~264,890,000 single point evaluations) across a wide swath of materials, surfaces, and adsorbates (nitrogen, carbon, and oxygen chemistries). We supplemented this dataset with randomly perturbed structures, short timescale molecular dynamics, and electronic structure analyses. The dataset comprises three central tasks indicative of day-to-day catalyst modeling and comes with pre-defined train/validation/test splits to facilitate direct comparisons with future model development efforts. We applied three state-of-the-art graph neural network models (CGCNN, SchNet, Dimenet++) to each of these tasks as baseline demonstrations for the community to build on. In almost every task, no upper limit on model size was identified, suggesting that even larger models are likely to improve on initial results. The dataset and baseline models are both provided as open resources, as well as a public leader board to encourage community contributions to solve these important tasks.

Single-atom catalysts (SACs) have emerged as frontiers for catalyzing chemical reactions, yet the diverse combinations of active elements and support materials, the nature of coordination environments, elude traditional methodologies in searching optimal SAC systems with superior catalytic performance. Herein, by integrating multi-branch Convolutional Neural Network (CNN) analysis models to hybrid descriptor based activity volcano plot, 2D SAC system composed of diverse metallic single atoms anchored on six type of 2D supports, including graphitic carbon nitride, nitrogen-doped graphene, graphene with dual-vacancy, black phosphorous, boron nitride, and C2N, are screened for efficient CO2RR. Starting from establishing a correlation map between the adsorption energies of intermediates and diverse electronic and elementary descriptors, sole singular descriptor lost magic to predict catalytic activity. Deep learning method utilizing multi-branch CNN model therefore was employed, using 2D electronic density of states as input to predict adsorption energies. Hybrid-descriptor enveloping both C- and O-types of CO2RR intermediates was introduced to construct volcano plots and limiting potential periodic table, aiming for intuitive screening of catalyst candidates for efficient CO2 reduction to CH4. The eDOS occlusion experiments were performed to unravel individual orbital contribution to adsorption energy. To explore the electronic scale principle governing practical engineering catalytic CO2RR activity, orbitalwise eDOS shifting experiments based on CNN model were employed. The study involves examining the adsorption energy and, consequently, catalytic activities while varying supported single atoms. This work offers a tangible framework to inform both theoretical screening and experimental synthesis, thereby paving the way for systematically designing efficient SACs.

Logical reading comprehension is a challenging task that entails grasping the underlying semantics of text and applying reasoning to deduce the correct answer. Prior researches have primarily focused on enhancing logical reasoning capabilities through Chain-of-Thought (CoT) or data augmentation. However, previous work constructing chain-of-thought rationales concentrates solely on analyzing correct options, neglecting the incorrect alternatives. Addtionally, earlier efforts on data augmentation by altering contexts rely on rule-based methods, which result in generated contexts that lack diversity and coherence. To address these issues, we propose a Premise-Oriented Data Augmentation (PODA) framework. This framework can generate CoT rationales including analyses for both correct and incorrect options, while constructing diverse and high-quality counterfactual contexts from incorrect candidate options. We integrate summarizing premises and identifying premises for each option into rationales. Subsequently, we employ multi-step prompts with identified premises to construct counterfactual context. To facilitate the model's capabilities to better differentiate the reasoning process associated with each option, we introduce a novel thought-path contrastive learning method that compares reasoning paths between the original and counterfactual samples. Experimental results on three representative LLMs demonstrate that our method can improve the baselines substantially across two challenging logical reasoning benchmarks (ReClor and LogiQA 2.0). The data and code are released at https://github.com/lalalamdbf/TPReasoner.

Recent advances in artificial intelligence (AI) have produced highly capable and controllable systems. This creates unprecedented opportunities for structured reasoning as well as collaboration among multiple AI systems and humans. To fully realize this potential, it is essential to develop a principled way of designing and studying such structured interactions. For this purpose, we introduce the conceptual framework of Flows: a systematic approach to modeling complex interactions. Flows are self-contained building blocks of computation, with an isolated state, communicating through a standardized message-based interface. This modular design allows Flows to be recursively composed into arbitrarily nested interactions, with a substantial reduction of complexity. Crucially, any interaction can be implemented using this framework, including prior work on AI--AI and human--AI interactions, prompt engineering schemes, and tool augmentation. We demonstrate the potential of Flows on the task of competitive coding, a challenging task on which even GPT-4 struggles. Our results suggest that structured reasoning and collaboration substantially improve generalization, with AI-only Flows adding +21 and human--AI Flows adding +54 absolute points in terms of solve rate. To support rapid and rigorous research, we introduce the aiFlows library. The library comes with a repository of Flows that can be easily used, extended, and composed into novel, more complex Flows. The aiFlows library is available at https://github.com/epfl-dlab/aiflows. Data and Flows for reproducing our experiments are available at https://github.com/epfl-dlab/cc_flows.

Scientific discovery contributes largely to human society's prosperity, and recent progress shows that LLMs could potentially catalyze this process. However, it is still unclear whether LLMs can discover novel and valid hypotheses in chemistry. In this work, we investigate this central research question: Can LLMs automatically discover novel and valid chemistry research hypotheses given only a chemistry research background (consisting of a research question and/or a background survey), without limitation on the domain of the research question? After extensive discussions with chemistry experts, we propose an assumption that a majority of chemistry hypotheses can be resulted from a research background and several inspirations. With this key insight, we break the central question into three smaller fundamental questions. In brief, they are: (1) given a background question, whether LLMs can retrieve good inspirations; (2) with background and inspirations, whether LLMs can lead to hypothesis; and (3) whether LLMs can identify good hypotheses to rank them higher. To investigate these questions, we construct a benchmark consisting of 51 chemistry papers published in Nature, Science, or a similar level in 2024 (all papers are only available online since 2024). Every paper is divided by chemistry PhD students into three components: background, inspirations, and hypothesis. The goal is to rediscover the hypothesis, given only the background and a large randomly selected chemistry literature corpus consisting the ground truth inspiration papers, with LLMs trained with data up to 2023. We also develop an LLM-based multi-agent framework that leverages the assumption, consisting of three stages reflecting the three smaller questions. The proposed method can rediscover many hypotheses with very high similarity with the ground truth ones, covering the main innovations.

This report overviews our ongoing work in enriching chain-of-thoughts datasets requiring arithmetical reasoning with the integration of non-parametric components, such as a calculator. We conduct an analysis of prominent relevant datasets such as GSM8K, Ape210K, AQuA-RAT, and MathQA and propose a machine-processable HTML-like format specifically tailored for working with semi-structured chains. By converting the datasets into this unified format, we enable the effective integration of large language models and symbolic systems, empowering them to tackle arithmetical reasoning tasks more efficiently.

Chain-of-Thought (CoT) reasoning has emerged as a promising approach for enhancing the performance of large language models (LLMs) on complex reasoning tasks. Recently, a series of studies attempt to explain the mechanisms underlying CoT, aiming to deepen the understanding of its efficacy. Nevertheless, the existing research faces two major challenges: (1) a lack of quantitative metrics to assess CoT capabilities and (2) a dearth of guidance on optimizing CoT performance. Motivated by this, in this work, we introduce a novel reasoning boundary framework (RBF) to address these challenges. To solve the lack of quantification, we first define a reasoning boundary (RB) to quantify the upper-bound of CoT and establish a combination law for RB, enabling a practical quantitative approach applicable to various real-world CoT tasks. To address the lack of optimization, we propose three categories of RBs. We further optimize these categories with combination laws focused on RB promotion and reasoning path optimization for CoT improvement. Through extensive experiments on 27 models and 5 tasks, the study validates the existence and rationality of the proposed framework. Furthermore, it explains the effectiveness of 10 CoT strategies and guides optimization from two perspectives. We hope this work can provide a comprehensive understanding of the boundaries and optimization strategies for reasoning in LLMs. Our code and data are available at https://github.com/LightChen233/reasoning-boundary.

Sparse autoencoders have recently produced dictionaries of high-dimensional vectors corresponding to the universe of concepts represented by large language models. We find that this concept universe has interesting structure at three levels: 1) The "atomic" small-scale structure contains "crystals" whose faces are parallelograms or trapezoids, generalizing well-known examples such as (man-woman-king-queen). We find that the quality of such parallelograms and associated function vectors improves greatly when projecting out global distractor directions such as word length, which is efficiently done with linear discriminant analysis. 2) The "brain" intermediate-scale structure has significant spatial modularity; for example, math and code features form a "lobe" akin to functional lobes seen in neural fMRI images. We quantify the spatial locality of these lobes with multiple metrics and find that clusters of co-occurring features, at coarse enough scale, also cluster together spatially far more than one would expect if feature geometry were random. 3) The "galaxy" scale large-scale structure of the feature point cloud is not isotropic, but instead has a power law of eigenvalues with steepest slope in middle layers. We also quantify how the clustering entropy depends on the layer.

RNA is a vital biomolecule with numerous roles and functions within cells, and interest in targeting it for therapeutic purposes has grown significantly in recent years. However, fully understanding and predicting RNA behavior, particularly for applications in drug discovery, remains a challenge due to the complexity of RNA structures and interactions. While foundational models in biology have demonstrated success in modeling several biomolecules, especially proteins, achieving similar breakthroughs for RNA has proven more difficult. Current RNA models have yet to match the performance observed in the protein domain, leaving an important gap in computational biology. In this work, we present ChaRNABERT, a suite of sample and parameter-efficient RNA foundational models, that through a learnable tokenization process, are able to reach state-of-the-art performance on several tasks in established benchmarks. We extend its testing in relevant downstream tasks such as RNA-protein and aptamer-protein interaction prediction. Weights and inference code for ChaRNABERT-8M will be provided for academic research use. The other models will be available upon request.

With the booming demand for machine learning applications, it has been recognized that the number of knowledgeable data scientists can not scale with the growing data volumes and application needs in our digital world. In response to this demand, several automated machine learning (AutoML) frameworks have been developed to fill the gap of human expertise by automating the process of building machine learning pipelines. Each framework comes with different heuristics-based design decisions. In this study, we present a comprehensive evaluation and comparison of the performance characteristics of six popular AutoML frameworks, namely, AutoWeka, AutoSKlearn, TPOT, Recipe, ATM, and SmartML, across 100 data sets from established AutoML benchmark suites. Our experimental evaluation considers different aspects for its comparison, including the performance impact of several design decisions, including time budget, size of search space, meta-learning, and ensemble construction. The results of our study reveal various interesting insights that can significantly guide and impact the design of AutoML frameworks.

The discovery of novel materials and functional molecules can help to solve some of society's most urgent challenges, ranging from efficient energy harvesting and storage to uncovering novel pharmaceutical drug candidates. Traditionally matter engineering -- generally denoted as inverse design -- was based massively on human intuition and high-throughput virtual screening. The last few years have seen the emergence of significant interest in computer-inspired designs based on evolutionary or deep learning methods. The major challenge here is that the standard strings molecular representation SMILES shows substantial weaknesses in that task because large fractions of strings do not correspond to valid molecules. Here, we solve this problem at a fundamental level and introduce SELFIES (SELF-referencIng Embedded Strings), a string-based representation of molecules which is 100\% robust. Every SELFIES string corresponds to a valid molecule, and SELFIES can represent every molecule. SELFIES can be directly applied in arbitrary machine learning models without the adaptation of the models; each of the generated molecule candidates is valid. In our experiments, the model's internal memory stores two orders of magnitude more diverse molecules than a similar test with SMILES. Furthermore, as all molecules are valid, it allows for explanation and interpretation of the internal working of the generative models.

Accurate potential energy surface (PES) descriptions are essential for atomistic simulations of materials. Universal machine learning interatomic potentials (UMLIPs)^{1-3} offer a computationally efficient alternative to density functional theory (DFT)^4 for PES modeling across the periodic table. However, their accuracy today is fundamentally constrained due to a reliance on DFT relaxation data.^{5,6} Here, we introduce MatPES, a foundational PES dataset comprising sim 400,000 structures carefully sampled from 281 million molecular dynamics snapshots that span 16 billion atomic environments. We demonstrate that UMLIPs trained on the modestly sized MatPES dataset can rival, or even outperform, prior models trained on much larger datasets across a broad range of equilibrium, near-equilibrium, and molecular dynamics property benchmarks. We also introduce the first high-fidelity PES dataset based on the revised regularized strongly constrained and appropriately normed (r^2SCAN) functional^7 with greatly improved descriptions of interatomic bonding. The open source MatPES initiative emphasizes the importance of data quality over quantity in materials science and enables broad community-driven advancements toward more reliable, generalizable, and efficient UMLIPs for large-scale materials discovery and design.

Graph neural networks (GNNs) have been used extensively for addressing problems in drug design and discovery. Both ligand and target molecules are represented as graphs with node and edge features encoding information about atomic elements and bonds respectively. Although existing deep learning models perform remarkably well at predicting physicochemical properties and binding affinities, the generation of new molecules with optimized properties remains challenging. Inherently, most GNNs perform poorly in whole-graph representation due to the limitations of the message-passing paradigm. Furthermore, step-by-step graph generation frameworks that use reinforcement learning or other sequential processing can be slow and result in a high proportion of invalid molecules with substantial post-processing needed in order to satisfy the principles of stoichiometry. To address these issues, we propose a representation-first approach to molecular graph generation. We guide the latent representation of an autoencoder by capturing graph structure information with the geometric scattering transform and apply penalties that structure the representation also by molecular properties. We show that this highly structured latent space can be directly used for molecular graph generation by the use of a GAN. We demonstrate that our architecture learns meaningful representations of drug datasets and provides a platform for goal-directed drug synthesis.

This position paper explores the rapid development of Foundation Models (FMs) in AI and their implications for intelligence and reasoning. It examines the characteristics of FMs, including their training on vast datasets and use of embedding spaces to capture semantic relationships. The paper discusses recent advancements in FMs' reasoning abilities which we argue cannot be attributed to increased model size but to novel training techniques which yield learning phenomena like grokking. It also addresses the challenges in benchmarking FMs and compares their structure to the human brain. We argue that while FMs show promising developments in reasoning and knowledge representation, understanding their inner workings remains a significant challenge, similar to ongoing efforts in neuroscience to comprehend human brain function. Despite having some similarities, fundamental differences between FMs and the structure of human brain warn us against making direct comparisons or expecting neuroscience to provide immediate insights into FM function.

The rapid advancement of ML models in critical sectors such as healthcare, finance, and security has intensified the need for robust data security, model integrity, and reliable outputs. Large multimodal foundational models, while crucial for complex tasks, present challenges in scalability, reliability, and potential misuse. Decentralized systems offer a solution by distributing workload and mitigating central points of failure, but they introduce risks of unauthorized access to sensitive data across nodes. We address these challenges with a comprehensive framework designed for responsible AI development. Our approach incorporates: 1) Zero-knowledge proofs for secure model verification, enhancing trust without compromising privacy. 2) Consensus-based verification checks to ensure consistent outputs across nodes, mitigating hallucinations and maintaining model integrity. 3) Split Learning techniques that segment models across different nodes, preserving data privacy by preventing full data access at any point. 4) Hardware-based security through trusted execution environments (TEEs) to protect data and computations. This framework aims to enhance security and privacy and improve the reliability and fairness of multimodal AI systems. Promoting efficient resource utilization contributes to more sustainable AI development. Our state-of-the-art proofs and principles demonstrate the framework's effectiveness in responsibly democratizing artificial intelligence, offering a promising approach for building secure and private foundational models.

We consider the prediction of the Hamiltonian matrix, which finds use in quantum chemistry and condensed matter physics. Efficiency and equivariance are two important, but conflicting factors. In this work, we propose a SE(3)-equivariant network, named QHNet, that achieves efficiency and equivariance. Our key advance lies at the innovative design of QHNet architecture, which not only obeys the underlying symmetries, but also enables the reduction of number of tensor products by 92\%. In addition, QHNet prevents the exponential growth of channel dimension when more atom types are involved. We perform experiments on MD17 datasets, including four molecular systems. Experimental results show that our QHNet can achieve comparable performance to the state of the art methods at a significantly faster speed. Besides, our QHNet consumes 50\% less memory due to its streamlined architecture. Our code is publicly available as part of the AIRS library (https://github.com/divelab/AIRS).

Efforts to overcome catastrophic forgetting have primarily centered around developing more effective Continual Learning (CL) methods. In contrast, less attention was devoted to analyzing the role of network architecture design (e.g., network depth, width, and components) in contributing to CL. This paper seeks to bridge this gap between network architecture design and CL, and to present a holistic study on the impact of network architectures on CL. This work considers architecture design at the network scaling level, i.e., width and depth, and also at the network components, i.e., skip connections, global pooling layers, and down-sampling. In both cases, we first derive insights through systematically exploring how architectural designs affect CL. Then, grounded in these insights, we craft a specialized search space for CL and further propose a simple yet effective ArchCraft method to steer a CL-friendly architecture, namely, this method recrafts AlexNet/ResNet into AlexAC/ResAC. Experimental validation across various CL settings and scenarios demonstrates that improved architectures are parameter-efficient, achieving state-of-the-art performance of CL while being 86%, 61%, and 97% more compact in terms of parameters than the naive CL architecture in Task IL and Class IL. Code is available at https://github.com/byyx666/ArchCraft.

Many challenging reasoning tasks require not just rapid, intuitive responses, but a more deliberate, multi-step approach. Recent progress in large language models (LLMs) highlights an important shift from the "System 1" way of quick reactions to the "System 2" style of reflection-and-correction problem solving. However, current benchmarks heavily rely on the final-answer accuracy, leaving much of a model's intermediate reasoning steps unexamined. This fails to assess the model's ability to reflect and rectify mistakes within the reasoning process. To bridge this gap, we introduce FINEREASON, a logic-puzzle benchmark for fine-grained evaluation of LLMs' reasoning capabilities. Each puzzle can be decomposed into atomic steps, making it ideal for rigorous validation of intermediate correctness. Building on this, we introduce two tasks: state checking, and state transition, for a comprehensive evaluation of how models assess the current situation and plan the next move. To support broader research, we also provide a puzzle training set aimed at enhancing performance on general mathematical tasks. We show that models trained on our state checking and transition data demonstrate gains in math reasoning by up to 5.1% on GSM8K.

Methods of computational quantum chemistry provide accurate approximations of molecular properties crucial for computer-aided drug discovery and other areas of chemical science. However, high computational complexity limits the scalability of their applications. Neural network potentials (NNPs) are a promising alternative to quantum chemistry methods, but they require large and diverse datasets for training. This work presents a new dataset and benchmark called nabla^2DFT that is based on the nablaDFT. It contains twice as much molecular structures, three times more conformations, new data types and tasks, and state-of-the-art models. The dataset includes energies, forces, 17 molecular properties, Hamiltonian and overlap matrices, and a wavefunction object. All calculations were performed at the DFT level (omegaB97X-D/def2-SVP) for each conformation. Moreover, nabla^2DFT is the first dataset that contains relaxation trajectories for a substantial number of drug-like molecules. We also introduce a novel benchmark for evaluating NNPs in molecular property prediction, Hamiltonian prediction, and conformational optimization tasks. Finally, we propose an extendable framework for training NNPs and implement 10 models within it.

sec:abstract Large Language Models (LLMs) have shown promise in assisting scientific discovery. However, such applications are currently limited by LLMs' deficiencies in understanding intricate scientific concepts, deriving symbolic equations, and solving advanced numerical calculations. To bridge these gaps, we introduce SciGLM, a suite of scientific language models able to conduct college-level scientific reasoning. Central to our approach is a novel self-reflective instruction annotation framework to address the data scarcity challenge in the science domain. This framework leverages existing LLMs to generate step-by-step reasoning for unlabelled scientific questions, followed by a process of self-reflective critic-and-revise. Applying this framework, we curated SciInstruct, a diverse and high-quality dataset encompassing mathematics, physics, chemistry, and formal proofs. We fine-tuned the ChatGLM family of language models with SciInstruct, enhancing their capabilities in scientific and mathematical reasoning. Remarkably, SciGLM consistently improves both the base model (ChatGLM3-6B-Base) and larger-scale models (12B and 32B), without sacrificing the language understanding capabilities of the base model. This makes SciGLM a suitable foundational model to facilitate diverse scientific discovery tasks. For the benefit of the wider research community, we release SciInstruct, SciGLM, alongside a self-reflective framework and fine-tuning code at https://github.com/THUDM/SciGLM.

The design of functional materials with desired properties is essential in driving technological advances in areas like energy storage, catalysis, and carbon capture. Generative models provide a new paradigm for materials design by directly generating entirely novel materials given desired property constraints. Despite recent progress, current generative models have low success rate in proposing stable crystals, or can only satisfy a very limited set of property constraints. Here, we present MatterGen, a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints. To enable this, we introduce a new diffusion-based generative process that produces crystalline structures by gradually refining atom types, coordinates, and the periodic lattice. We further introduce adapter modules to enable fine-tuning towards any given property constraints with a labeled dataset. Compared to prior generative models, structures produced by MatterGen are more than twice as likely to be novel and stable, and more than 15 times closer to the local energy minimum. After fine-tuning, MatterGen successfully generates stable, novel materials with desired chemistry, symmetry, as well as mechanical, electronic and magnetic properties. Finally, we demonstrate multi-property materials design capabilities by proposing structures that have both high magnetic density and a chemical composition with low supply-chain risk. We believe that the quality of generated materials and the breadth of MatterGen's capabilities represent a major advancement towards creating a universal generative model for materials design.

The Four-Element Theory is a fundamental framework in criminal law, defining the constitution of crime through four dimensions: Subject, Object, Subjective aspect, and Objective aspect. This theory is widely referenced in legal reasoning, and many Large Language Models (LLMs) attempt to incorporate it when handling legal tasks. However, current approaches rely on LLMs' internal knowledge to incorporate this theory, often lacking completeness and representativeness. To address this limitation, we introduce JUREX-4E, an expert-annotated knowledge base covering 155 criminal charges. It is structured through a progressive hierarchical annotation framework that prioritizes legal source validity and employs diverse legal interpretation methods to ensure comprehensiveness and authority. We evaluate JUREX-4E on the Similar Charge Distinction task and apply it to Legal Case Retrieval, demonstrating its effectiveness in improving LLM performance. Experimental results validate the high quality of JUREX-4E and its substantial impact on downstream legal tasks, underscoring its potential for advancing legal AI applications. Code: https://github.com/THUlawtech/JUREX

Molecular conformation optimization is crucial to computer-aided drug discovery and materials design. Traditional energy minimization techniques rely on iterative optimization methods that use molecular forces calculated by a physical simulator (oracle) as anti-gradients. However, this is a computationally expensive approach that requires many interactions with a physical simulator. One way to accelerate this procedure is to replace the physical simulator with a neural network. Despite recent progress in neural networks for molecular conformation energy prediction, such models are prone to distribution shift, leading to inaccurate energy minimization. We find that the quality of energy minimization with neural networks can be improved by providing optimization trajectories as additional training data. Still, it takes around 5 times 10^5 additional conformations to match the physical simulator's optimization quality. In this work, we present the Gradual Optimization Learning Framework (GOLF) for energy minimization with neural networks that significantly reduces the required additional data. The framework consists of an efficient data-collecting scheme and an external optimizer. The external optimizer utilizes gradients from the energy prediction model to generate optimization trajectories, and the data-collecting scheme selects additional training data to be processed by the physical simulator. Our results demonstrate that the neural network trained with GOLF performs on par with the oracle on a benchmark of diverse drug-like molecules using 50x less additional data.