Surmounting the multiple-minima problem in protein folding

Protein folding is a very difficult global optimization problem. Furthermor e it is coupled with the difficult task of designing a reliable force field with which one has to search for the global minimum. A summary of a series of optimization methods developed and applied to various problems involvin g polypeptide chains is described in this paper. With recent developments, a computational treatment of the folding of globular proteins of up to 140 residues is shown to be tractable.