title: Macromolecular Entropy Can Be Accurately Computed from Force.
abstract: A method is presented to evaluate a molecule's entropy from the atomic forces calculated in a molecular dynamics simulation. Specifically, diagonalization of the mass-weighted force covariance matrix produces eigenvalues which in the harmonic approximation can be related to vibrational frequencies. The harmonic oscillator entropies of each vibrational mode may be summed to give the total entropy. The results for a series of hydrocarbons, dialanine and a β hairpin are found to agree much better with values derived from thermodynamic integration than results calculated using quasiharmonic analysis. Forces are found to follow a harmonic distribution more closely than coordinate displacements and better capture the underlying potential energy surface. The method's accuracy, simplicity, and computational similarity to quasiharmonic analysis, requiring as input force trajectories instead of coordinate trajectories, makes it readily applicable to a wide range of problems.
authors.affiliation: ETH Zürich , Biosystems Science and Engineering, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Ulf
authors.initials: U
authors.lastname: Hensen
authors.affiliation: Heidelberg Institute for Theoretical Studies , Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Gräter
authors.affiliation: Manchester Institute of Biotechnology, The University of Manchester , 131 Princess Street, Manchester M1 7DN, United Kingdom.|School of Chemistry, The University of Manchester , Oxford Road, Manchester M13 9PL, United Kingdom.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Henchman