Improved docking of peptides and small molecules in iMOLSDOCK

iMOLSDOCK is an induced-fit docking algorithm that uses the mutually orthogonal Latin squares (MOLS) sampling technique. Here, we describe the updates made to iMOLSDOCK in order to increase receptor flexibility, improve the scoring system, and speed up calculation. With a dataset of 35 peptide-protein complexes, the PepSet benchmark dataset of 80 peptide-protein complexes, and the Astex Diverse set, which uses nonpeptide small molecules as ligands, iMOLSDOCK has been benchmarked and validated. Flexible residues are now able to deviate from the starting position by a maximum of 3.0 Å due to the increased receptor flexibility. The ranking effectiveness of iMOLSDOCK has increased by 24% once the scoring system was improved. Additionally, iMOLSDOCK has been compared to Gold v5.2.1, HPEPDOCK, AutoDock CrankPep v1.0, AutoDock Vina, HADDOCK, PatchDock, and RosettaLigand. For induced-fit peptide-protein docking, iMOLSDOCK achieved success rates of 6%, 37%, and 89% at the top 1, 10, and 100 levels. At the top 1, 10, and 100 levels, iMOLSDOCK had success rates for small molecule-protein docking of 14%, 31%, and 49%. The computation time for peptide docking was lowered by two orders of magnitude, and for nonpeptide small molecule docking, it was roughly 14 times faster due to code optimization in the iMOLSDOCK docking tool. Source code and binary of iMOLSDOCK could be obtained from https://sourceforge.net/projects/mols2-0/files/ .