Comparison of three preprocessing filters efficiency in virtual screening: identification of new putative LXRbeta regulators as a test case

Leo Ghemtio 1 Marie-Dominique Devignes 1 Malika Smaïl-Tabbone 1 Michel Souchet 1 Vincent Leroux 1 Bernard Maigret 1, *
* Corresponding author
1 ORPAILLEUR - Knowledge representation, reasonning
INRIA Lorraine, LORIA - Laboratoire Lorrain de Recherche en Informatique et ses Applications
Abstract : In silico screening methodologies are widely recognized as efficient approaches in early steps of drug discovery. However, in the virtual high-throughput screening (VHTS) context, where hit compounds are searched among millions of candidates, three-dimensional comparison techniques and knowledge discovery from databases should offer a better efficiency to finding novel drug leads than those of computationally expensive molecular dockings. Therefore, the present study aims at developing a filtering methodology to efficiently eliminate unsuitable compounds in VHTS process. Several filters are evaluated in this paper. The first two are structure-based and rely on either geometrical docking or pharmacophore depiction. The third filter is ligand-based and uses knowledge-based and fingerprint similarity techniques. These filtering methods were tested with the Liver X Receptor (LXR) as a target of therapeutic interest, as LXR is a key regulator in maintaining cholesterol homeostasis. The results show that the three considered filters are complementary so that their combination should generate consistent compound lists of potential hits.
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Submitted on : Saturday, December 18, 2010 - 1:18:47 AM
Last modification on : Thursday, January 11, 2018 - 6:19:54 AM

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  • HAL Id : hal-00547968, version 1
  • PUBMED : 20420434

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Leo Ghemtio, Marie-Dominique Devignes, Malika Smaïl-Tabbone, Michel Souchet, Vincent Leroux, et al.. Comparison of three preprocessing filters efficiency in virtual screening: identification of new putative LXRbeta regulators as a test case. Journal of Chemical Information and Modeling, American Chemical Society, 2010, 50 (5), pp.701-715. ⟨hal-00547968⟩

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