Simultaneous and coupled energy optimization of homologous proteins: a new tool for structure prediction.
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.
Keasar
C
C
Department of Physical Chemistry, Fritz Haber Research Center for Molecular Dynamics, Hebrew University, Givaat Ram, Jerusalem, Israel.
Elber
R
R
Skolnick
J
J
D000595:Amino Acid Sequence; D006728:Hormones / Q000737:chemistry*; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D006728:Hormones