Preparing ligand structures. We generated ligand structures for docking based on the ligands provided by PDBbind. To avoid biasing poses toward the crystal structures, and in contrast to previously reported studies, we discarded the native compound conformation and generated a UFF energy-minimized starting conformation from the ligand SMILES supplied by the PDB using RDKit . This approach better reflects commercial vHTS campaigns, where a crystal pose or experimental structure of the ligand is typically lacking.