Novel protocols for modeling flexible loops: Implications for drug design

COMP 250

Karen A. Rossi,, Carolyn A. Weigelt,, Akbar Nayeem,, and Stanley R. Krystek Jr., Computer-Assisted Drug Design, Bristol-Myers Squibb Company, P.O. Box 5400, Princeton, NJ 08543-5400
The accurate modeling of loops is one of the key challenges in protein structure modeling. This is especially true in cases where protein loop conformations change based upon ligand binding. Several examples are known in the literature where the size and shape of a protein binding pocket changes when comparing the Apo structure to protein complexes with diverse ligands. In this study, we examine a series of therapeutically relevant protein structures that contain loops that exhibit significant ligand-dependent conformational changes. Two methods for generating accurate loop conformations for these proteins are described; an improved protocol for induced fit docking, Sample-IFD-Refine (SIR) and a new method, Delete-Dock-Resample (DDR).

Poster Session
6:00 PM-8:00 PM, Tuesday, August 18, 2009 Walter E. Washington Convention Center -- Ballroom A, Poster

Division of Computers in Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009