Effective and rapid bioactivity profiling using pharmacophore-based parallel screening

CINF 17

Theodora M. Steindl, Theodora.Steindl@uibk.ac.at1, Daniela Schuster2, Johannes Kirchmair, kirchmair@inteligand.com3, Remy Hoffmann, remy@accelrys.com4, Christian Laggner, Christian.Laggner@uibk.ac.at2, Gerhard Wolber, wolber@inteligand.com3, and Thierry Langer, thierry.langer@uibk.ac.at2. (1) Computer-Aided Molecular Design Group, University of Innsbruck, Innrain 52c, Innsbruck, A-6020, Austria, (2) Department of Pharmaceutical Chemistry, Computer Aided Molecular Design Group, University of Innsbruck, Institute of Pharmacy, Innrain 52c, Innsbruck, A-6020, Austria, (3) Inte:Ligand GmbH, Clemens Maria Hofbauer-G. 6, 2344 Maria Enzersdorf, Austria, (4) Accelrys, Parc Club Orsay Universite, 20, rue Jean Rostand, Orsay, 91898, France
3D Pharmacophore-based parallel screening is introduced as an in silico method to predict the potential biological activities of potential drug molecules. This study presents an application example employing a Pipeline Pilot-based screening platform and a collection of structure-based pharmacophore models built using the LigandScout software for automatic large-scale virtual activity profiling. An extensive set of HIV protease inhibitor pharmacophore models was used to screen different test sets consisting of active and inactive compounds. In addition, we investigated, whether it is possible in a parallel screening system to differentiate between similar molecules / molecules acting on closely related proteins, and therefore we incorporated a collection of other protease inhibitors including aspartic protease inhibitors. The results of the screening experiments show a clear trend towards an enhanced signal to noise ratio (true positives/false positives and true negatives/false negatives).
 

Drug Reprofiling
2:00 PM-5:40 PM, Sunday, August 19, 2007 BCEC -- 252 A, Oral

Division of Chemical Information

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007