Minimum free energy pathways and free energy profiles for conformational transitions based on atomistic molecular dynamics simulations.

An efficient method for the calculation of minimum free energy pathways and free energy profiles for conformational transitions is presented. Short restricted perturbation-targeted molecular dynamics trajectories are used to generate an approximate free energy surface. Approximate reaction pathways for the conformational change are constructed from one-dimensional line segments on this surface using a Monte Carlo optimization. Accurate free energy profiles are then determined along the pathways by means of one-dimensional adaptive umbrella sampling simulations. The method is illustrated by its application to the alanine "dipeptide." Due to the low computational cost and memory demands, the method is expected to be useful for the treatment of large biomolecular systems.