C Keasar1, R Elber, J Skolnick. 1. Department of Physical Chemistry, Fritz Haber Research Center for Molecular Dynamics, Hebrew University, Givaat Ram, Jerusalem, Israel.
Abstract
BACKGROUND: Homology-based modeling and global optimization of energy are two complementary approaches to prediction of protein structures. A combination of the two approaches is proposed in which a novel component is added to the energy and forces similarity between homologous proteins. RESULTS: The combination was tested for two families: pancreatic hormones and homeodomains. The simulated lowest-energy structure of the pancreatic hormones is a reasonable approximation to the native fold. The lowest-energy structure of the homeodomains has 80% of the native contacts, but the helices are not packed correctly. The fourth lowest energy structure of the homeodomains has the correct helix packing (RMS 5.4 A and 82% of the correct contacts). Optimizations of a single protein of the family yield considerably worse structures. CONCLUSIONS: Use of coupled homologous proteins in the search for the native fold is more successful than the folding of a single protein in the family.
BACKGROUND: Homology-based modeling and global optimization of energy are two complementary approaches to prediction of protein structures. A combination of the two approaches is proposed in which a novel component is added to the energy and forces similarity between homologous proteins. RESULTS: The combination was tested for two families: pancreatic hormones and homeodomains. The simulated lowest-energy structure of the pancreatic hormones is a reasonable approximation to the native fold. The lowest-energy structure of the homeodomains has 80% of the native contacts, but the helices are not packed correctly. The fourth lowest energy structure of the homeodomains has the correct helix packing (RMS 5.4 A and 82% of the correct contacts). Optimizations of a single protein of the family yield considerably worse structures. CONCLUSIONS: Use of coupled homologous proteins in the search for the native fold is more successful than the folding of a single protein in the family.