Multidimensional free‐energy calculations using the weighted histogram analysis method

TLDR

WHAM extends Ferrenberg and Swendsen's multiple histogram technique for free‑energy and potential‑of‑mean‑force calculations. The authors illustrate WHAM by computing a two‑dimensional potential‑of‑mean‑force surface for deoxyadenosine dihedrals using Monte Carlo simulations with AMBER force fields, and the method also analyzes statistical accuracy and guides efficient simulation usage. WHAM offers a major advantage over umbrella sampling techniques. © 1995 John Wiley & Sons, Inc.

Abstract

Abstract The recently formulated weighted histogram analysis method (WHAM) 1 is an extension of Ferrenberg and Swendsen's multiple histogram technique for free‐energy and potential of mean force calculations. As an illustration of the method, we have calculated the two‐dimensional potential of mean force surface of the dihedrals gamma and chi in deoxyadenosine with Monte Carlo simulations using the all‐atom and united‐atom representation of the AMBER force fields. This also demonstrates one of the major advantages of WHAM over umbrella sampling techniques. The method also provides an analysis of the statistical accuracy of the potential of mean force as well as a guide to the most efficient use of additional simulations to minimize errors. © 1995 John Wiley & Sons, Inc.