Influence of protonation states in protein side chain and loop conformation

COMP 242

Gabriela Barreiro, gabriela.barreiro@gmail.com1, Ben Sellers, sellersb@gmail.com2, and Matthew P. Jacobson, matt.jacobson@ucsf.edu1. (1) Department of Pharmaceutical Chemistry, University of California, San Francisco, 600 16th Street, Room N472C, Box 2240, San Francisco, CA 94143, (2) Graduate Group in Biophysics, University of California, San Francisco, 600 16th Street, Room N472, San Francisco, CA 94143
Protonation states of ionizable residues play an important role in protein structure and function. We have observed that alternative protonation states due to local shifts in pKa can affect the accuracy of computational side chain and loop prediction methods. We have addressed this issue by developing a new algorithm to optimize the protonation state of titratable groups. This new algorithm is integrated with our hierarchical approach to all-atom protein loop prediction such that protonation states are evaluated simultaneously with conformational sampling using the OPLS-AA force field and the Surface Generalized Born solvent model. We have selected high resolution X-ray structures with ionizable residues embedded in short loops (up to 7 residues) that were calculated to have shifted pKa values. Preliminary results show improvements in side chain and loop prediction accuracy when the correct protonation state is accounted for.
 

Poster Session
6:00 PM-8:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Computers in Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006