Calculation of protein conformation by global optimization of a potential energy function

Jooyoung Lee 1, Adam Liwo 1 2, Daniel R. Ripoll 3, Jaroslaw Pillardy 1, Harold A. Scheraga 1 *

1Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 2Faculty of Chemistry, University of Gdask, Gdask, Poland 3Cornell Theory Center, Ithaca, New York

^*Correspondence to Harold A. Scheraga, Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301.

Conference: Third Meeting on the Critical Assessment of Techniques for Protein Structure Prediction (CASP3), Asilomar, California, December 1998

Funded by:
 National Science Foundation; Grant Number: MCB95-13167
 National Institutes of Health; Grant Number: GM-14312
 Polish State Committee for Scientific Research, KBN.; Grant Number: 3T09A 102/16
 National Foundation for Cancer Research

 

Keywords

protein folding; global optimization; conformational search; potential energy function; structure prediction

 

Abstract

A novel hierarchical approach to protein folding has been applied to compute the unknown structures of seven target proteins provided by CASP3. The approach is based exclusively on the global optimization of a potential energy function for a united-residue model by conformational space annealing, followed by energy refinement using an all-atom potential. Comparison of the submitted models for five globular proteins with the experimental structures shows that the conformations of large fragments (60 aa) were predicted with rmsds of 4.2-6.8 Å for the C atoms. Our lowest-energy models for targets T0056 and T0061 were particularly successful, producing the correct fold of approximately 52% and 80% of the structures, respectively. These results support the thermodynamic hypothesis that protein structure can be computed solely by global optimization of a potential energy function for a given amino acid sequence. Proteins Suppl 1999;3:204-208. © 1999 Wiley-Liss, Inc.