MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening

@article{citeulike:2651285, abstract = {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.CONCLUSIONS: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.}, author = {Sauton, Nicolas and Lagorce, David and Villoutreix, Bruno and Miteva, Maria }, citeulike-article-id = {2651285}, doi = {10.1186/1471-2105-9-184}, journal = {BMC Bioinformatics}, keywords = {docking}, number = {1}, posted-at = {2008-04-28 10:52:35}, priority = {2}, title = {MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening}, url = {http://dx.doi.org/10.1186/1471-2105-9-184}, volume = {9}, year = {2008} }

TY - JOUR ID - citeulike:2651285 L3 - citeulike-article-id:2651285 TI - MS-DOCK: Accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening JF - BMC Bioinformatics VL - 9 IS - 1 N2 - 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.CONCLUSIONS: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. KW - docking AU - Sauton, Nicolas AU - Lagorce, David AU - Villoutreix, Bruno AU - Miteva, Maria PY - 2008/// UR - http://dx.doi.org/10.1186/1471-2105-9-184 ER -