Model systems for docking

COMP 47

Brian Shoichet, Pharmaceutical Chemistry, Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, San Francisco, CA 94143-2240
Molecular docking is widely used to screen large compound collections for novel lead molecules that complement a receptor of known structure. Docking energy functions are approximate and many degrees of freedom are under-sampled. To understand where algorithms can be improved, we have turned to model systems where predictions can be tested in detail. We are using both highly simplified, cavity sites in T4 lysozyme, slightly more complicted cavity-like sites that are also open to solvent at one end, and full "drug-like" binding sites, the latter in b-lactamase. Predicted ligands are being tested for binding, geometry, and protein motion using x-ray crystallography. We hope to use this cycle of theory development and testing in a range of simple and more complicated sites to understand some of the weaknesses in our current docking algorithms, and to improve them.
 

Docking and Scoring
9:00 AM-12:20 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- 109A, Oral

Division of Computers in Chemistry

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