On the relative merits of equilibrium and non-equilibrium simulations for the estimation of free-energy differences

Daura, Xavier, Affentranger, Roman and Mark, Alan E. (2010) On the relative merits of equilibrium and non-equilibrium simulations for the estimation of free-energy differences. ChemPhysChem, 11 17: 3734-3743. doi:10.1002/cphc.201000562

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads

Author Daura, Xavier
Affentranger, Roman
Mark, Alan E.
Title On the relative merits of equilibrium and non-equilibrium simulations for the estimation of free-energy differences
Journal name ChemPhysChem   Check publisher's open access policy
ISSN 1439-4235
1439-7641
Publication date 2010-12-01
Year available 2010
Sub-type Article (original research)
DOI 10.1002/cphc.201000562
Open Access Status DOI
Volume 11
Issue 17
Start page 3734
End page 3743
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Language eng
Abstract The possibility of estimating equilibrium free-energy profiles from multiple non-equilibrium simulations using the fluctuation-dissipation theory or the relation proposed by Jarzynski has attracted much attention. Although the Jarzynski estimator has poor convergence properties for simulations far from equilibrium, corrections have been derived for cases in which the work is Gaussian distributed. Here, we examine the utility of corrections proposed by Gore and collaborators using a simple dissipative system as a test case. The system consists of a single methane-like particle in explicit water. The Jarzynski equality is used to estimate the change in free energy associated with pulling the methane particle a distance of 3.9 nm at rates ranging from similar to 0.1 to 100 ms(-1). It is shown that although the corrections proposed by Gore and collaborators have excellent numerical performance, the profiles still converge slowly. Even when the corrections are applied in an ideal case where the work distribution is necessarily Gaussian, performing simulations under quasi-equilibrium conditions is still most efficient. Furthermore, it is shown that even for a single methane molecule in water, pulling rates as low as 1 ms(-1) can be problematic. The implications of this finding for studies in which small molecules or even large biomolecules are pulled through inhomogeneous environments at similar pulling rates are discussed.
Formatted abstract
The possibility of estimating equilibrium free-energy profiles from multiple non-equilibrium simulations using the fluctuation-dissipation theory or the relation proposed by Jarzynski has attracted much attention. Although the Jarzynski estimator has poor convergence properties for simulations far from equilibrium, corrections have been derived for cases in which the work is Gaussian distributed. Here, we examine the utility of corrections proposed by Gore and collaborators using a simple dissipative system as a test case. The system consists of a single methane-like particle in explicit water. The Jarzynski equality is used to estimate the change in free energy associated with pulling the methane particle a distance of 3.9 nm at rates ranging from 0.1 to 100 m s-1. It is shown that although the corrections proposed by Gore and collaborators have excellent numerical performance, the profiles still converge slowly. Even when the corrections are applied in an ideal case where the work distribution is necessarily Gaussian, performing simulations under quasi-equilibrium conditions is still most efficient. Furthermore, it is shown that even for a single methane molecule in water, pulling rates as low as 1 m s-1 can be problematic. The implications of this finding for studies in which small molecules or even large biomolecules are pulled through inhomogeneous environments at similar pulling rates are discussed.Moving targets: A simple dissipative system is used to test the merits of performing equilibrium or non-equilibrium simulations to estimate free-energy differences. For moving a single methane molecule in water (see picture), where the work distribution is Gaussian, simulating under quasi-equilibrium conditions is most efficient. For non-equilibrium approaches, pulling rates as low as 1 nm ns-1 are problematic, casting doubt on the validity of many studies involving biomolecules. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keyword Computational chemistry
Equilibrium/nonequilibrium simulations
Free-energy difference
Molecular dynamics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID BIO2007-62954
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 7 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 16 Jan 2011, 10:10:24 EST