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MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening
BACKGROUND: The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373571/ https://www.ncbi.nlm.nih.gov/pubmed/18402678 http://dx.doi.org/10.1186/1471-2105-9-184 |
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author | Sauton, Nicolas Lagorce, David Villoutreix, Bruno O Miteva, Maria A |
author_facet | Sauton, Nicolas Lagorce, David Villoutreix, Bruno O Miteva, Maria A |
author_sort | Sauton, Nicolas |
collection | PubMed |
description | BACKGROUND: The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of targets with millions of molecules is intractable to most laboratories nor indeed desirable. Since shape complementarity is of primary importance for most protein-ligand interactions, we have developed a tool/protocol based on rigid-body docking to select compounds that fit well into binding sites. RESULTS: Here we present an efficient multiple conformation rigid-body docking approach, MS-DOCK, which is based on the program DOCK. This approach can be used as the first step of a multi-stage docking/scoring protocol. First, we developed and validated the Multiconf-DOCK tool that generates several conformers per input ligand. Then, each generated conformer (bioactives and 37970 decoys) was docked rigidly using DOCK6 with our optimized protocol into seven different receptor-binding sites. MS-DOCK was able to significantly reduce the size of the initial input library for all seven targets, thereby facilitating subsequent more CPU demanding flexible docking procedures. CONCLUSION: MS-DOCK can be easily used for the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening protocol in order to shorten computation times. |
format | Text |
id | pubmed-2373571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-23735712008-05-08 MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening Sauton, Nicolas Lagorce, David Villoutreix, Bruno O Miteva, Maria A BMC Bioinformatics Methodology Article BACKGROUND: The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of targets with millions of molecules is intractable to most laboratories nor indeed desirable. Since shape complementarity is of primary importance for most protein-ligand interactions, we have developed a tool/protocol based on rigid-body docking to select compounds that fit well into binding sites. RESULTS: Here we present an efficient multiple conformation rigid-body docking approach, MS-DOCK, which is based on the program DOCK. This approach can be used as the first step of a multi-stage docking/scoring protocol. First, we developed and validated the Multiconf-DOCK tool that generates several conformers per input ligand. Then, each generated conformer (bioactives and 37970 decoys) was docked rigidly using DOCK6 with our optimized protocol into seven different receptor-binding sites. MS-DOCK was able to significantly reduce the size of the initial input library for all seven targets, thereby facilitating subsequent more CPU demanding flexible docking procedures. CONCLUSION: MS-DOCK can be easily used for the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening protocol in order to shorten computation times. BioMed Central 2008-04-10 /pmc/articles/PMC2373571/ /pubmed/18402678 http://dx.doi.org/10.1186/1471-2105-9-184 Text en Copyright © 2008 Sauton et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Methodology Article Sauton, Nicolas Lagorce, David Villoutreix, Bruno O Miteva, Maria A MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title | MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title_full | MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title_fullStr | MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title_full_unstemmed | MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title_short | MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
title_sort | ms-dock: accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening |
topic | Methodology Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373571/ https://www.ncbi.nlm.nih.gov/pubmed/18402678 http://dx.doi.org/10.1186/1471-2105-9-184 |
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