MULTIDIMENSIONAL FREE-ENERGY CALCULATIONS USING THE WEIGHTED HISTOGRAM ANALYSIS METHOD

The recently formulated weighted histogram analysis method (WHAM)(1) i s an extension of Ferrenberg and Swendsen's multiple histogram techniq ue for free-energy and potential of mean force calculations. As an ill ustration of the method, we have calculated the two-dimensional potent ial of mean force surface of the dihedrals gamma and chi in deoxyadeno sine with Monte Carlo simulations using the all-atom and united-atom r epresentation of the AMBER force fields. This also demonstrates one of the major advantages of WHAM over umbrella sampling techniques. The m ethod also provides an analysis of the statistical accuracy of the pot ential of mean force as well as a guide to the most efficient use of a dditional simulations to minimize errors. (C) 1995 by John Wiley & Son s, Inc.