Journal of Molecular Modeling

, Volume 14, Issue 2, pp 135–148

Multiple-step virtual screening using VSM-G: overview and validation of fast geometrical matching enrichment

Authors

  • Alexandre Beautrait
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Vincent Leroux
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Matthieu Chavent
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Léo Ghemtio
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Marie-Dominique Devignes
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Malika Smaïl-Tabbone
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
  • Wensheng Cai
    • Department of ChemistryNankai University
  • Xuegang Shao
    • Department of ChemistryNankai University
  • Gilles Moreau
  • Peter Bladon
    • Interprobe Chemical Services
  • Jianhua Yao
    • Laboratory of Computer Chemistry and ChemoinformaticsShanghai Institute of Organic Chemistry
    • Nancy UniversitéLORIA, Groupe ORPAILLEUR
Original Paper

DOI: 10.1007/s00894-007-0257-9

Cite this article as:
Beautrait, A., Leroux, V., Chavent, M. et al. J Mol Model (2008) 14: 135. doi:10.1007/s00894-007-0257-9

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.

https://static-content.springer.com/image/art%3A10.1007%2Fs00894-007-0257-9/MediaObjects/894_2007_257_Figa_HTML.gif
Figure

Basic principle of the virtual screening funnel process.

Keywords

Multiple-step virtual screeningVSM-GStructure-based drug designGeometrical matchingSpherical harmonics surfacesSHEFGOLDMolecular database enrichment

Copyright information

© Springer-Verlag 2007