The recombined molecules were compared against two sets of ligands: (i) the 542 ligands, from which the reduced set of 624 fragments originated (reduced original ligands), were searched for exact and substructure matches and (ii) the ChEMBL database was screened for exact matches and the most similar molecules. From the latter, all 1,870,461 molecules from the ChEMBL 25 34 dataset were downloaded. If an entry contained a mixture, the largest molecule was extracted. Duplicates were dropped (based on canonical SMILES) and only molecules with more than 4 heavy atoms were kept. Molecules were standardized and neutralized 36 using RDKit's rdMolStandardize module,