Applications of simulated annealing to the conformational analysis of flexible molecules

Abstract

Abstract We describe in this article our solution to the global minimum problem which uses the simulated annealing algorithm of Kirkpatrick. This method is a Metropolis ( e ‐Δ E / kT ) Monte Carlo sampling of conformation space with simultaneous constraint of the search by lowering the temperature T so that the search converges on the global minimum. The Anneal‐Conformer program has been extensively tested with peptides and organic molecules using either the Amber or MM2 force fields. A history file of the simulated annealing process allows reconstruction of the random walk in conformation space for subsequent examination. Thus plots of distance and dihedral angle changes during the search for the global minimum can be examined to deduce molecular shape and flexibility. A separate program Conf‐Gen reads the history file and extracts all low energy conformations visited during the run.