Comparative Virtual Screening of IDH1-R132H Inhibitors

The crystal structures of the IDH1^R132H in complex with an inhibitor were downloaded from the PDB database (http://www.rcsb.org), including 4UMX, 5L57, 5L58, 5LGE, 5SUN, 5SVF, 5TQH, 6ADG, and 6B0Z. For each complex, the Protein Preparation Wizard module in Schrödinger 2015 (Schrödinger, LLC, New York, NY, 2015) was applied to add hydrogen and missing side chains, remove all water molecules, assign protonation states and partial charges through OPLS2005 force field (Jorgensen et al., 1996 (link)), and minimize all heavy atoms until the root-mean-square deviation (RMSD) was reached ≤0.3 Å.
To evaluate the virtual screening capability of different crystal structures, 423 actives were directly extracted from the PubChem database and served as a validation data set (https://pubchem.ncbi.nlm.nih.gov/bioassay/1344832#section=Top), and their decoys, generated by DUD•E (Mysinger et al., 2012 (link)), were considered as a decoy data set. In total, 23,900 decoys were generated.