SIMULATED ANNEALING OF A PROTEIN IN A CONTINUUM SOLVENT BY MULTIPLE-TIME-STEP MOLECULAR-DYNAMICS

In this paper we present a computationally efficient means of performi ng simulated annealing on atomic level protein structures. The method which is based upon a Trotter factorization of the classical Liouville propagator is employed in a series of simulated annealing studies of a small protein using a standard molecular mechanics type potential as well as a continuum approximation to include the effects of solvation . Preliminary results are presented for the performance of the potenti al using standard force field parametrizations in attempts to distingu ish native-like structures from those that are distinctly non-native. Low-energy structures with large rms deviations from the minimized X-r ay structure were found, thereby suggesting the possibility that the p otentials employed in this work may not be of sufficient accuracy to d istinguish the native protein structure.