Addressing the speed/accuracy dilemma of the virtual screening process

CINF 51

Pascal Bonnet, pbonnet@prdbe.jnj.com1, Eric Arnoult2, and Christophe Meyer, cmeyer2@prdfr.jnj.com2. (1) Molecular Informatics, Johnson & Johnson PRD, A division of Janssen-Pharmaceutica, Turnhoutseweg 30, 2340 Beerse, Belgium, (2) Molecular Informatics, Janssen-Cilag S.A, Campus de Maigremont, 27106 Val de Reuil, France
Virtual screening is employed by most pharmaceutical companies to screen in-silico large collections of compounds in order to identify new hits to biological targets. Several computational tools are available but speed and accuracy are still a major concern. To relieve the limitations of this technique while improving the quality of its outcome, we describe here a sequential steps process implemented on a GRID-computing platform. This tool was applied to large-scale database mining and intensive scoring computations to enable the identification of the best candidates for biological testing. A first optional filter is applied to remove non drug-like compounds, followed by a 3D-pharmacophore search. The remaining compounds are docked in the protein binding site then rescored with an accurate scoring function using a combined molecular dynamics/continuum solvent potential. All the computationally intensive steps have been grid-enabled to accelerate the process. Three case studies with high enrichment factor are presented.
 

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Chemical Information

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006