Optimal intermediates in staged free energy calculations
- Department of Chemical Engineering, State University of New York at Buffalo, Buffalo, New York 14260-4200 (United States)
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.}
- OSTI ID:
- 362669
- Journal Information:
- Journal of Chemical Physics, Vol. 111, Issue 10; Other Information: PBD: Sep 1999
- Country of Publication:
- United States
- Language:
- English
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