Lately, to overcome the molecular size limitation within benchmark QM datasets, several efforts have been made to generate datasets that comprehensively explore the conformational space of large and flexible molecules along with their associated QM properties calculated in gas phase or solvent, see Table . For instance, the QMugs 38 collection comprises 19 QM properties of circa 2 M gas-phase conformers of 665, 911 molecules with up to 100 non-hydrogen atoms computed using ωB97X-D density functional and the def2-SVP basis set. The OE62 dataset covers 61, 489 molecules with up to 92 non-hydrogen atoms that were optimized in gas phase using PBE(tight) level of theory supplemented with Tkatchenko-Scheffler van der Waals (TS) interaction . This dataset also contains 3 QM properties for 30, 876 structures evaluated using PBE0(tight) level of theory together with implicit water defined by the Multipole Expansion (MPE) model . Regarding the vast GEOM collection, , only 1.3 M conformers corresponding to 1, 511 BACE molecules were generated considering molecule-solvent interactions described by ALPB implicit solvent model of water. From here, 455, 000 conformers of 534 BACE molecules were selected and used for further geometry optimization calculations using r2scan-3c functional with C-PCM implicit model of water and, posteriorly, 6 QM properties were collected. Moreover, Eastman et al. have recently introduced the SPICE dataset that explicitly considers the interaction between the molecule and water molecules via Amber14 classical force field to get 1, 300 (equilibrium and non-equilibrium) structures of 26 amino acids. Energies, atomic forces, and other 6 QM properties were computed using the ωB97M-D3(BJ) functional and def2-TZVPPD basis set. Despite these efforts, challenges remain to enable a better understanding of solvent effects as well as collective dispersion interactions in the chemical space of large drug-like molecules, including: (i) assessing the accuracy and reliability of QM structures and properties with respect to the employed density-functional approximation, especially for larger and more flexible molecules in which van der Waals (vdW) and molecule-solvent interactions are stronger, (ii) offering a large set of molecular (global) and atom-in-a-molecule (local) physicochemical properties that would enable a comprehensive exploration of these interactions in structure-property and property-property relationships throughout chemical space, and (iii) providing accurate and reliable QM data that will enable the construction of models for describing covalent and non-covalent vdW interactions in large (solvated) molecules.