THE MULTIPLE-MINIMA PROBLEM IN PROTEIN FOLDING

Abstract

The conformational energy surface of a polypeptide or protein has many local minima, and conventional energy minimization procedures reach only a local minimum (near the starting point of the optimization algorithm) instead of the global minimum (the multiple‐minima problem). Several procedures have been developed to surmount this problem, the most promising of which are: (a) build up procedure, (b) optimization of electrostatics, (c) Monte Carlo‐plus‐energy minimization, (d) electrostatically‐driven Monte Carlo, (e) inclusion of distance restraints, (f) adaptive importance‐sampling Monte Carlo, (g) relaxation of dimensionality, (h) pattern‐recognition, and (i) diffusion equation method. These procedures have been applied to a variety of polypeptide structural problems, and the results of such computations are presented. These include the computation of the structures of open‐chain and cyclic peptides, fibrous proteins and globular proteins. Present efforts are being devoted to scaling up these procedures...