Protein - Small Molecule docking with receptor flexibility in iMOLSDOCK

TL;DR

The paper extends the iMOLSDOCK technique for flexible receptor docking to nonpeptide small molecules, benchmarking it against other tools and demonstrating superior accuracy despite higher computational cost.

Contribution

It introduces an extension of iMOLSDOCK for nonpeptide ligands and validates its effectiveness against established docking tools.

Findings

iMOLSDOCK outperforms GOLD and AutoDock Vina in accuracy

The method effectively models receptor flexibility during docking

The source code is publicly available for use and further development.

Abstract

We have earlier reported the iMOLSDOCK technique to perform induced-fit peptide-protein docking. iMOLSDOCK uses the mutually orthogonal Latin squares (MOLS) technique to sample the conformation and the docking pose of the small molecule ligand and also the flexible residues of the receptor protein, and arrive at the optimum pose and conformation. In this paper we report the extension carried out in iMOLSDOCK to dock nonpeptide small molecule ligands to receptor proteins. We have benchmarked and validated iMOLSDOCK with a dataset of 34 protein-ligand complexes with nonpeptide small molecules as ligands. We have also compared iMOLSDOCK with other flexible receptor docking tools GOLD v5.2.1 and AutoDock Vina. The results obtained show that the method works better than these two algorithms, though it consumes more computer time. The source code and binary of MOLS 2.0 (under a GNU Lesser General Public License) are freely available for download at https://sourceforge.net/projects/mols2-0/files/