Molecules for this work were compiled from several sources, including 88,106 organic compounds from the Crystallographic Open Database, 9,10 3,009,591 from PubChemQC, 88,550 molecules from the Pitt Quantum Repository, and previous work on conformational flexibility, which included 70,850 molecules from a subset of ZINC 37 and 4,378 molecules from the Platinum ligand database. For all sources, the largest substructure was retained (i.e. solvent or salts were removed from the crystallographic unit cells). For compounds without initial 3D coordinates, Open Babel 3.1 was used to generate initial coordinates, since CREST requires an initial geometry. As noted above, the total set of compounds included more than 3 million unique molecules. Properties across the data sets are illustrated in Figures , S3, and S4 and are roughly comparable to the Platinum diverse set and the DrugBank approved set, with the exception that the PubChemQC set compounds are smaller.