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

  • Alexandre Beautrait
  • Vincent Leroux
  • Matthieu Chavent
  • Léo Ghemtio
  • Marie-Dominique Devignes
  • Malika Smaïl-Tabbone
  • Wensheng Cai
  • Xuegang Shao
  • Gilles Moreau
  • Peter Bladon
  • Jianhua Yao
  • Bernard Maigret
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
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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.

Figure

Basic principle of the virtual screening funnel process.

Keywords

Multiple-step virtual screening VSM-G Structure-based drug design Geometrical matching Spherical harmonics surfaces SHEF GOLD Molecular database enrichment 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Alexandre Beautrait
    • 1
  • Vincent Leroux
    • 1
  • Matthieu Chavent
    • 1
  • Léo Ghemtio
    • 1
  • Marie-Dominique Devignes
    • 1
  • Malika Smaïl-Tabbone
    • 1
  • Wensheng Cai
    • 2
  • Xuegang Shao
    • 2
  • Gilles Moreau
    • 3
  • Peter Bladon
    • 4
  • Jianhua Yao
    • 5
  • Bernard Maigret
    • 1
  1. 1.Nancy UniversitéLORIA, Groupe ORPAILLEURVandœuvre-lès-Nancy CedexFrance
  2. 2.Department of ChemistryNankai UniversityTianjinPeople’s Republic of China
  3. 3.CharantonFrance
  4. 4.Interprobe Chemical ServicesGlasgowUK
  5. 5.Laboratory of Computer Chemistry and ChemoinformaticsShanghai Institute of Organic ChemistryShanghaiPeople’s Republic of China

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