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Title: Optimal intermediates in staged free energy calculations

Abstract

We examine the precision of free energy perturbation (FEP) methods of molecular simulation. We develop a quantitative model of the calculation in terms of the so-called {ital f} and {ital g} distributions that characterize the energies sampled in a FEP calculation. The model is then re-expressed in terms of the entropy difference between the systems of interest, and the variance of the {ital g} distribution. We apply the model to analyze the optimization of multistage insertion free energy calculations, and reach a quantitative criterion for minimizing the overall variance. The analysis indicates that the appropriate heuristic for optimizing the choice of intermediates is to select them to equalize the {ital entropy} differences among all stages of the overall FEP calculation. A more accurate criterion is specified, but in practice it differs little from this simpler one. We illustrate our conclusions by conducting two-stage FEP calculations using Monte Carlo simulations on Lennard-Jones (LJ) systems at several temperatures and two densities. The LJ systems differ in the presence of a single LJ particle, and the intermediate is defined to have a single hard sphere of diameter that can be used to optimize the two-stage FEP calculation. The model provides an excellent descriptionmore » of the precision of the FEP calculations. {copyright} {ital 1999 American Institute of Physics.}« less

Authors:
;  [1]
  1. Department of Chemical Engineering, State University of New York at Buffalo, Buffalo, New York 14260-4200 (United States)
Publication Date:
OSTI Identifier:
362669
Resource Type:
Journal Article
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 111; Journal Issue: 10; Other Information: PBD: Sep 1999
Country of Publication:
United States
Language:
English
Subject:
40 CHEMISTRY; ENTROPY; FREE ENERGY; OPTIMIZATION; MONTE CARLO METHOD; LENNARD-JONES POTENTIAL; SIMULATION; SAMPLING; LIQUIDS

Citation Formats

Lu, N., and Kofke, D.A. Optimal intermediates in staged free energy calculations. United States: N. p., 1999. Web. doi:10.1063/1.479206.
Lu, N., & Kofke, D.A. Optimal intermediates in staged free energy calculations. United States. doi:10.1063/1.479206.
Lu, N., and Kofke, D.A. Wed . "Optimal intermediates in staged free energy calculations". United States. doi:10.1063/1.479206.
@article{osti_362669,
title = {Optimal intermediates in staged free energy calculations},
author = {Lu, N. and Kofke, D.A.},
abstractNote = {We examine the precision of free energy perturbation (FEP) methods of molecular simulation. We develop a quantitative model of the calculation in terms of the so-called {ital f} and {ital g} distributions that characterize the energies sampled in a FEP calculation. The model is then re-expressed in terms of the entropy difference between the systems of interest, and the variance of the {ital g} distribution. We apply the model to analyze the optimization of multistage insertion free energy calculations, and reach a quantitative criterion for minimizing the overall variance. The analysis indicates that the appropriate heuristic for optimizing the choice of intermediates is to select them to equalize the {ital entropy} differences among all stages of the overall FEP calculation. A more accurate criterion is specified, but in practice it differs little from this simpler one. We illustrate our conclusions by conducting two-stage FEP calculations using Monte Carlo simulations on Lennard-Jones (LJ) systems at several temperatures and two densities. The LJ systems differ in the presence of a single LJ particle, and the intermediate is defined to have a single hard sphere of diameter that can be used to optimize the two-stage FEP calculation. The model provides an excellent description of the precision of the FEP calculations. {copyright} {ital 1999 American Institute of Physics.}},
doi = {10.1063/1.479206},
journal = {Journal of Chemical Physics},
number = 10,
volume = 111,
place = {United States},
year = {1999},
month = {9}
}