Evaluating the Accuracy of the Quasiharmonic Approximation

Abstract

The quasiharmonic approximation (QH) allows the configurational entropy of a molecule to be estimated on the basis of a molecular dynamics simulation, through construction of a Gaussian probability distribution of conformations with variances equal to those provided by the simulation. At its introduction in 1981, the QH method was successfully applied to simple molecular systems with only one highly occupied energy well, and fluctuations were analyzed in a system of internal bond-angle-torsion coordinates. However, more recent studies have applied the QH method to complex biomolecular systems and have relied upon Cartesian coordinates. The present study evaluates the accuracy of the QH method through comparisons with more detailed methods. The chief findings are that the QH method can markedly overestimate the configurational entropy for systems with multiple occupied energy wells and that such errors tend to be magnified by the use of Cartesian coordinates instead of bond-angle-torsion coordinates.