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Guest lecture by Bernard Maigret

We are happy to announce the following guest lecture:

The VSM-G (Virtual Screening Manager for computational Grids) project: example of use for the identification of new cholecystokinine-type 1 receptor antagonists
CNRS director Barnard Maigret, Nancy, France

Thursday 15 January 2009 at 1515
Seminar room B2.U002, Rikshospitalet

Abstract: The VSM-G platform, dedicated to automated high-throughput screening using worldwide-distributed cluster grids, will be presented during this talk. VSM-G is a Java-based integrated package constituted of pre-processing engines for both protein targets and small molecules putative ligands to be screened on, and of several screening procedures. Both ligand- and receptor-based approaches are available within the platform. The latter uses a funnel docking strategy and is architectured as a sequence of different docking modules ranging from a fast but less accurate surface-matching procedure for crude rigid docking to slower but more elaborated molecular dynamics calculations. At each step of the funnel and depending on tuning, a small proportion of molecules can be prioritized as more promising, discarding or delaying supposedly inappropriate candidates. VSM-G is able to handle several millions of compounds versus hundreds of targets (which can be different targets or several conformations of same one, e.g. extracted from molecular dynamics sampling or NMR data)), yielding to a small set of putative hit compounds to be proposed for real biological testing. Because considerable computing power is needed for performing large-scale searches of this type within a reasonable time, VSM-G incorporates the possible use of computational grid technology, especially for the fast-matching procedure used in the first selection docking filter As an example to highlight the VSM-G concept and interest, the high-throughput virtual screening experiment presented in this talk aimed to identify, from a database consisting of about 4,000,000 drugable molecules, putative hits for the CCK1 receptor which belongs to the GPCRs family. At the end of this experience, we were able proposes a short list of only 13 molecules to be really tested by a pharmaceutical company partner (Mayo Clinic, US), and two of these compounds where shown to be active, a very good ratio indeed. Several perspectives for expanding VSM-G functionality, some of which are currently developed, will also be discussed.

Hosts: Ute Krengel & Torbjørn Rognes

 

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