title: Multiple-step virtual screening using VSM-G: overview and validation of fast geometrical matching enrichment.
abstract: Numerous methods are available for use as part of a virtual screening strategy but, as yet, no single method is able to guarantee both a level of confidence comparable to experimental screening and a level of computing efficiency that could drastically cut the costs of early phase drug discovery campaigns. Here, we present VSM-G (virtual screening manager for computational grids), a virtual screening platform that combines several structure-based drug design tools. VSM-G aims to be as user-friendly as possible while retaining enough flexibility to accommodate other in silico techniques as they are developed. In order to illustrate VSM-G concepts, we present a proof-of-concept study of a fast geometrical matching method based on spherical harmonics expansions surfaces. This technique is implemented in VSM-G as the first module of a multiple-step sequence tailored for high-throughput experiments. We show that, using this protocol, notable enrichment of the input molecular database can be achieved against a specific target, here the liver-X nuclear receptor. The benefits, limitations and applicability of the VSM-G approach are discussed. Possible improvements of both the geometrical matching technique and its implementation within VSM-G are suggested.
authors.affiliation: Nancy Université, LORIA, Groupe ORPAILLEUR, Campus scientifique, BP 239, 54506 Vandoeuvre-lès-Nancy Cedex, France. bernard.maigret@loria.fr
authors.forename: Alexandre
authors.initials: A
authors.lastname: Beautrait
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroux
authors.forename: Matthieu
authors.initials: M
authors.lastname: Chavent
authors.forename: Léo
authors.initials: L
authors.lastname: Ghemtio
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Devignes
authors.forename: Malika
authors.initials: M
authors.lastname: Smaïl-Tabbone
authors.forename: Wensheng
authors.initials: W
authors.lastname: Cai
authors.forename: Xuegang
authors.initials: X
authors.lastname: Shao
authors.forename: Gilles
authors.initials: G
authors.lastname: Moreau
authors.forename: Peter
authors.initials: P
authors.lastname: Bladon
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yao
authors.forename: Bernard
authors.initials: B
authors.lastname: Maigret
mesh_terms: D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands