9513167 Scheraga This work is a three-part attack on the protein folding problem. First, the statistical mechanics of the problem will be elucidated. Simplified lattice models of proteins (with realistic but easily computable procedures) will be used to provide fundamental statistical mechanical insight into the protein folding problem. The Entropy Sampling Monte Carlo method (augmented by a conformational-biased chain regrowth procedure and a jump-walking method) is used to determine the density of states of the protein, from which the properties related to conformation and folding are reduced. The method is being extended to an off-lattice treatment. Second, in order to be able to use energy as a criterion to distinguish the global minimum from other local minima in the multidimensional energy surface (the so-called multiple-minima problem), a new force field is being developed. Third, the multiple-minima problem is being surmounted by the diffusion equation method. %%% This theoretical approach will provide the basic understanding of the folding properties of protein. This problem is currently at the frontier of protein research. The basic understanding to be acquired will be applicable to the biotechnology industry. Finally, this approach will provide training for the research associates carrying out this research, and also for several graduate students working together with these research associates. ***
