Basic ingredients of free energy calculations: A review

Christ, Clara D., Mark, Alan E. and van Gunsteren, Wilfred F. (2010) Basic ingredients of free energy calculations: A review. Journal of Computational Chemistry, 31 8: 1569-1582. doi:10.1002/jcc.21450

Author Christ, Clara D.
Mark, Alan E.
van Gunsteren, Wilfred F.
Title Basic ingredients of free energy calculations: A review
Journal name Journal of Computational Chemistry   Check publisher's open access policy
ISSN 0192-8651
Publication date 2010-06-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/jcc.21450
Open Access Status Not yet assessed
Volume 31
Issue 8
Start page 1569
End page 1582
Total pages 14
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
Abstract Methods to compute free energy differences between different states of a molecular system are reviewed with the aim of identifying their basic ingredients and their utility when applied in practice to biomolecular systems. A free energy calculation is comprised of three basic components: (i) a suitable model or Hamiltonian, (ii) a sampling protocol with which one can generate a representative ensemble of molecular configurations, and (iii) an estimator of the free energy difference itself. Alternative sampling protocols can be distinguished according to whether one or more states are to be sampled. In cases where only a single state is considered, six alternative techniques could be distinguished: (i) changing the dynamics, (ii) deforming the energy surface, (iii) extending the dimensionality, (iv) perturbing the forces, (v) reducing the number of degrees of freedom, and (vi) multi-copy approaches. In cases where multiple states are to be sampled, the three primary techniques are staging, importance sampling, and adiabatic decoupling. Estimators of the free energy can be classified as global methods that either count the number of times a given state is sampled or use energy differences. Or, they can be classified as local methods that either make use of the force or are based on transition probabilities. Finally, this overview of the available techniques and how they can be best used in a practical context is aimed at helping the reader choose the most appropriate combination of approaches for the biomolecular system, Hamiltonian and free energy difference of interest. © 2009 Wiley Periodicals, Inc.
Keyword Free energy
Molecular simulation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 200020-121913
Institutional Status UQ
Additional Notes Published online 23 December 2009. Alternate title: Feature article: Basic ingredients of free energy calculations: A review.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 169 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 183 times in Scopus Article | Citations
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Created: Sun, 23 May 2010, 10:02:45 EST