Improving docking enrichments by picking "the right pose"


Hans E. Purkey, Erik Evensen, Kenneth E. Lind, and Erin K. Bradley. Computational Sciences, Sunesis Pharmaceuticals Inc, 341 Oyster Point Blvd., South San Francisco, CA 94080
Docking methods often generate small molecule poses that are close to crystallographically determined binding positions. Even though much effort has gone into improving scoring functions, existing scoring functions typically do not rank order candidate poses correctly. We present a complementary approach in which experimental results are used to generate models for activity that are then used to select among docking poses. We investigate whether ligand positions that lie at this intersection of two manifolds (the docking conformational space and experimentally-informed pharmacophore and shape spaces) improve compound selection by available scoring functions or by their application alone. We will present examples of this method applied to both public soluble ligand datasets and internal datasets obtained from several protein targets using TetheringSM.

Docking and Scoring
1:30 PM-5:20 PM, Sunday, August 22, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004