TY - JOUR
T1 - Comparison of free energy methods for molecular systems
AU - Ytreberg, F. Marty
AU - Swendsen, Robert H.
AU - Zuckerman, Daniel M.
N1 - Funding Information:
The authors would like to thank Ron White and Hagai Meirovitch for valuable discussions, and also Manuel Athènes and Gilles Adjanor for helpful comments regarding the manuscript. Funding for this research was provided by the Department of Computational Biology and the Department of Environmental and Occupational Health at the University of Pittsburgh, and the National Institutes of Health under Fellowship No. GM073517 [to one of the authors (F.M.Y.)] and Grant Nos. ES007318, GM073517, and CA078039.
PY - 2006
Y1 - 2006
N2 - We present a detailed comparison of computational efficiency and precision for several free energy difference (ΔF) methods. The analysis includes both equilibrium and nonequilibrium approaches, and distinguishes between unidirectional and bidirectional methodologies. We are primarily interested in comparing two recently proposed approaches, adaptive integration, and single-ensemble path sampling to more established methodologies. As test cases, we study relative solvation free energies of large changes to the size or charge of a Lennard-Jones particle in explicit water. The results show that, for the systems used in this study, both adaptive integration and path sampling offer unique advantages over the more traditional approaches. Specifically, adaptive integration is found to provide very precise long-simulation ΔF estimates as compared to other methods used in this report, while also offering rapid estimation of ΔF. The results demonstrate that the adaptive integration approach is the best overall method for the systems studied here. The single-ensemble path sampling approach is found to be superior to ordinary Jarzynski averaging for the unidirectional, "fast-growth" nonequilibrium case. Closer examination of the path sampling approach on a two-dimensional system suggests it may be the overall method of choice when conformational sampling barriers are high. However, it appears that the free energy landscapes for the systems used in this study have rather modest configurational sampling barriers.
AB - We present a detailed comparison of computational efficiency and precision for several free energy difference (ΔF) methods. The analysis includes both equilibrium and nonequilibrium approaches, and distinguishes between unidirectional and bidirectional methodologies. We are primarily interested in comparing two recently proposed approaches, adaptive integration, and single-ensemble path sampling to more established methodologies. As test cases, we study relative solvation free energies of large changes to the size or charge of a Lennard-Jones particle in explicit water. The results show that, for the systems used in this study, both adaptive integration and path sampling offer unique advantages over the more traditional approaches. Specifically, adaptive integration is found to provide very precise long-simulation ΔF estimates as compared to other methods used in this report, while also offering rapid estimation of ΔF. The results demonstrate that the adaptive integration approach is the best overall method for the systems studied here. The single-ensemble path sampling approach is found to be superior to ordinary Jarzynski averaging for the unidirectional, "fast-growth" nonequilibrium case. Closer examination of the path sampling approach on a two-dimensional system suggests it may be the overall method of choice when conformational sampling barriers are high. However, it appears that the free energy landscapes for the systems used in this study have rather modest configurational sampling barriers.
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U2 - 10.1063/1.2378907
DO - 10.1063/1.2378907
M3 - Article
C2 - 17115745
AN - SCOPUS:33750970530
SN - 0021-9606
VL - 125
JO - Journal of Chemical Physics
JF - Journal of Chemical Physics
IS - 18
M1 - 184114
ER -