• Linux: SEEKR2 runs on Linux machines, necessitating a working knowledge of Linux commands. Users should be comfortable navigating the Linux file systems, executing commands with the Linux environment, and managing files using the terminal interface. • Anaconda: Experience with Anaconda, a popular package manager and environment management system, is required for installing SEEKR2. Users should be familiar with creating new conda environments, managing and installing conda packages, and activating or deactivating environments as necessary. • MD simulations using OpenMM: Prior experience in running MD simulations using the OpenMM engine is crucial for effectively utilizing SEEKR2. Users should have a substantial understanding of MD simulation principles, such as force fields, integrators, and simulation parameters and their implementation in the OpenMM simulation engine . • Force field parameterization using Amber: It is beneficial for users to be familiar with AmberTools, especially with Amber's antechamber and LEaP programs for force field parameterization and system preparation, respectively. LEaP is essential for system preparation, including solvation, ion addition, and force field assignment, while the antechamber program is employed for parameterizing small molecules. Familiarity with these tools ensures smooth integration into the SEEKR2 workflow . • Research collaboratory for structural bioinformatics (RCSB) protein data bank: To initiate a SEEKR2 simulation, users need a Protein Data Bank (PDB) file, which can be obtained from the RCSB Protein Data Bank (). Users should be familiar with searching for specific PDB files and downloading them from the database for use in SEEKR2 simulations. Alternatively, one may obtain structures or systems already prepared for simulation from collaborators or a previous study.