Coupling the folding of homologous proteins

Coupling the folding of homologous proteins

^*Department of Physical Chemistry, Department of Biological Chemistry, Fritz Haber Research Center for Molecular Dynamics and Wolfson Center for Applied Structural Biology, Hebrew University, Givat Ram Jerusalem 91904, Israel; ^†Department of Structural Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305; and ^§Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037

Abstract

The empirical observation that homologous proteins fold to similar structures is used to enhance the capabilities of an ab initio algorithm to predict protein conformations. A penalty function that forces homologous proteins to look alike is added to the potential and is employed in the coupled energy optimization of several homologous proteins. Significant improvement in the quality of the computed structures (as compared with the computational folding of a single protein) is demonstrated and discussed.

Footnotes

↵ ‡ To whom reprint requests should be addressed. e-mail ron{at}fh.huji.ac.il.
This paper was presented at the colloquium “Computational Biomolecular Science,” organized by Russell Doolittle, J. Andrew McCammon, and Peter G. Wolynes, held September 11–13, 1997, sponsored by the National Academy of Sciences at the Arnold and Mabel Beckman Center in Irvine, CA.
ABBREVIATIONS:

LMCP,

Lattice Monte Carlo program;

RMSD,

root mean square difference