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 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.
Sauton
Nicolas
N
INSERM, U648, 45 rue des Sts Peres, University Paris Descartes, 75006 Paris, France. nicolas.sauton@laposte.net
Lagorce
David
D
Villoutreix
Bruno O
BO
Miteva
Maria A
MA
D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D016208:Databases, Factual; D007536:Isomerism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010316:Particle Size; D011485:Protein Binding; D014584:User-Computer Interface
D008024:Ligands