MS-DOCK: accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening.
BMC Bioinformatics
; 9: 184, 2008 Apr 10.
Article
en En
| MEDLINE
| ID: mdl-18402678
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Unión Proteica
/
Interfaz Usuario-Computador
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Biología Computacional
/
Conformación Molecular
Tipo de estudio:
Diagnostic_studies
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Guideline
/
Prognostic_studies
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Screening_studies
Idioma:
En
Revista:
BMC Bioinformatics
Asunto de la revista:
INFORMATICA MEDICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Francia