Monte Carlo-minimization approach to the multiple-minima problem in protein folding.

Abstract

A Monte Carlo-minimization method has been developed to overcome the multiple-minima problem. The Metropolis Monte Carlo sampling, assisted by energy minimization, surmounts intervening barriers in moving through successive discrete local minima in the multidimensional energy surface. The method has located the lowest-energy minimum thus far reported for the brain pentapeptide [Met5]enkephalin in the absence of water. Presumably it is the global minimum-energy structure. This supports the concept that protein folding may be a Markov process. In the presence of water, the molecules appear to exist as an ensemble of different conformations.