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

A novel hierarchical approach to protein folding has been applied to comput e the unknown structures of seven target proteins provided by CASP3. The ap proach is based exclusively on the global optimization of a potential energ y function for a united-residue model by conformational space annealing, fo llowed by energy refinement using an all-atom potential. Comparison of the submitted models for five globular proteins with the experimental structure s shows that the conformations of large fragments (similar to 60 aa) were p redicted with rmsds of 4.2-6.8 Angstrom for the C-alpha atoms. Our lowest-e nergy models for targets T0056 and T0061 were particularly successful, prod ucing the correct fold of approximately 52% and 80% of the structures, resp ectively These results support the thermodynamic hypothesis that protein st ructure can be computed solely by global optimization of a potential energy function for a given amino acid sequence. (C) 1999 Wiley-Liss, Inc.