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An Introduction to Best Practices in Free Energy Calculations

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Biomolecular Simulations

Part of the book series: Methods in Molecular Biology ((MIMB,volume 924))

Abstract

Free energy calculations are extremely useful for investigating small-molecule biophysical properties such as protein-ligand binding affinities and partition coefficients. However, these calculations are also notoriously difficult to implement correctly. In this chapter, we review standard methods for computing free energy via simulation, discussing current best practices and examining potential pitfalls for computational researchers performing them for the first time. We include a variety of examples and tips for how to set up and conduct these calculations, including applications to relative binding affinities and small-molecule solvation free energies.

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Acknowledgements

The authors wish to thank John Chodera (UC-Berkeley) for ongoing discussions of reliability and usability for free energy calculations as well as TriPham (UVa) and Justin Lemkul (Virginia Tech), Joe Allen (SUNY Stonybrook) for careful review of the manuscript.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Virginia, Charlottesville, VA, USA

    Michael R. Shirts

  2. Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA

    David L. Mobley

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  1. Michael R. Shirts
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  2. David L. Mobley
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Correspondence to Michael R. Shirts .

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Editors and Affiliations

  1. DSIMB, UMR-S 665, INSERM, rue Alexandre Cabanel 6, Paris, 75015, France

    Luca Monticelli

  2. , Department of Applied Physics, Aalto University, Otakaari, AALTO, FI-00076, Finland

    Emppu Salonen

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Shirts, M.R., Mobley, D.L. (2013). An Introduction to Best Practices in Free Energy Calculations. In: Monticelli, L., Salonen, E. (eds) Biomolecular Simulations. Methods in Molecular Biology, vol 924. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-017-5_11

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  • DOI: https://doi.org/10.1007/978-1-62703-017-5_11

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-016-8

  • Online ISBN: 978-1-62703-017-5

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