Improvement in structure model accuracy and molecular replacement through high-resolution protein structure refinement

COMP 181

Bin Qian, bqian@u.washington.edu, Biochemistry, University of Washington, Health Science Building, Seattle, WA 98195 and David Baker, dabaker@u.washington.edu, Biochemistry, University of Washington/ HHMI, 15th and Pacific, Seattle, WA 98195.
We describe a new approach to refining protein structure models that focuses sampling in regions most likely to contain errors while allowing the whole structure to relax in a physically realistic all atom force field. Convergence on the global energy minimum is enhanced by an evolution-inspired iterative procedure which balances intensification of the search in the lowest energy explored regions with diversification to maintain subpopulations exploring alternative energy minima. We show that the refinement protocol can significantly improve the accuracy of comparative models based on structures of remote homologues and models produced using NMR data, and that the refined models often yield significantly better solutions to the x-ray crystallographic phase problem in molecular replacement tests.
 

Computational Science & Engineering Advances Supported by NSF Resource
1:30 PM-5:15 PM, Monday, August 20, 2007 BCEC -- 156B, Oral

Division of Computers in Chemistry

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