We additionally assessed the quality and diversity of the complexes and the ligands in the benchmark sets (Figure and Supporting Information, Tables ). The resolution and DPI values of the CS405 complexes are globally higher than in CSKDE95, but the selection of 244 complexes out of the CS405 set improves the median resolution and DPI of the structures (Figure and 5B, resp.). The ligand EDIAm values of the CSKDE95 and the CS244 sets are comparable, with 4 (4%) resp. 17 (7%) cases below 0.4, which are potentially problematic as docking references (5C). The RMSD values between randomized and native ligand structures without (Figure ) and with (Figure ) superimposition show that our randomization procedure generated notably different ligands geometries, except for small rigid ligands. Randomization of the ligands in CS244 yields higher RMSD values than in CSKDE95, as the former presents ligands with more rotatable dihedrals (Figure ). On average, ligands from CS244 are less buried than ligands from CSKDE95 (Figure ). They are more likely to carry a positive charge than a negative charge (Figure ), and they are more likely to present crystal contacts than the ligands in CSKDE95 (Figure ).