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

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...

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Autores principales: Bell, Eric W., Zhang, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556049/
https://www.ncbi.nlm.nih.gov/pubmed/31175455
http://dx.doi.org/10.1186/s13321-019-0362-7
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author Bell, Eric W.
Zhang, Yang
author_facet Bell, Eric W.
Zhang, Yang
author_sort Bell, Eric W.
collection PubMed
description 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.
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spelling pubmed-65560492019-06-13 DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism Bell, Eric W. Zhang, Yang J Cheminform Research Article 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. Springer International Publishing 2019-06-07 /pmc/articles/PMC6556049/ /pubmed/31175455 http://dx.doi.org/10.1186/s13321-019-0362-7 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Bell, Eric W.
Zhang, Yang
DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title_full DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title_fullStr DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title_full_unstemmed DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title_short DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism
title_sort dockrmsd: an open-source tool for atom mapping and rmsd calculation of symmetric molecules through graph isomorphism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556049/
https://www.ncbi.nlm.nih.gov/pubmed/31175455
http://dx.doi.org/10.1186/s13321-019-0362-7
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