Enveloping distribution sampling: A method to calculate free energy differences from a single simulation


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Date

2007-05-14

Publication Type

Journal Article

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Abstract

The authors present a method to calculate free energy differences between two states A and B “on the fly” from a single molecular dynamics simulation of a reference state R. No computer time has to be spent on the simulation of intermediate states. Only one state is sampled, i.e., the reference state R which is designed such that the subset of phase space important to it is the union of the parts of phase space important to A and B. Therefore, an accurate estimate of the relative free energy can be obtained by construction. The authors applied the method to four test systems dipole inversion, van der Waals interaction perturbation, charge inversion, and water to methanol conversion and compared the results to thermodynamic integration estimates. In two cases, the enveloping distribution sampling calculation was straightforward. However, in the charge inversion and the water to methanol conversion, Hamiltonian replica-exchange molecular dynamics of the reference state was necessary to observe transitions in the reference state simulation between the parts of phase space important to A and B, respectively. This can be explained by the total absence of phase space overlap of A and B in these two cases.

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published

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Volume

126 (18)

Pages / Article No.

184110

Publisher

American Institute of Physics

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Subject

Water; Liquid structure; Organic compounds; Sampling methods; Free energy; Molecular dynamics method; Liquid theory

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03304 - Van Gunsteren, Wilfred F. (emeritus) check_circle

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