Journal Article

DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism

Bell, Eric W., Zhang, Yang

2019

Overview

Comparison of ligand poses generated by protein–ligand docking programs has often been carried out with the assumption of direct atomic correspondence between ligand structures. However, this correspondence is not necessarily chemically relevant for symmetric molecules and can lead to an artificial inflation of ligand pose distance metrics, particularly those that depend on receptor superposition (rather than ligand superposition), such as docking root mean square deviation (RMSD). Several of the commonly-used RMSD calculation algorithms that correct for molecular symmetry do not take into account the bonding structure of molecules and can therefore result in non-physical atomic mapping. Here, we present DockRMSD, a docking pose distance calculator that converts the symmetry correction to a graph isomorphism searching problem, in which the optimal atomic mapping and RMSD calculation are performed by an exhaustive and fast matching search of all isomorphisms of the ligand structure graph. We show through evaluation of docking poses generated by AutoDock Vina on the CSAR Hi-Q set that DockRMSD is capable of deterministically identifying the minimum symmetry-corrected RMSD and is able to do so without significant loss of computational efficiency compared to other methods. The open-source DockRMSD program can be conveniently integrated with various docking pipelines to assist with accurate atomic mapping and RMSD calculations, which can therefore help improve docking performance, especially for ligand molecules with complicated structural symmetry.

• Publisher: Springer International Publishing,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Algorithms / Analysis / Caffeine / Chemical bonds / Chemistry / Chemistry and Materials Science / Computational Biology/Bioinformatics / Computational efficiency / Computer applications / Computer Applications in Chemistry / Docking / Documentation and Information in Chemistry / Inflation (Economics) / Isomorphism / Ligand pose comparison / Ligands / Mapping / Mathematical analysis / Molecular structure / Open source software / Organic chemistry / Protein–ligand docking / Research Article / Superposition (mathematics) / Symmetric molecules / Symmetry / Theoretical and Computational Chemistry