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Calculation of Binding Free Energies

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Book cover Molecular Modeling of Proteins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1215))

Abstract

Molecular dynamics simulations enable access to free energy differences governing the driving force underlying all biological processes. In the current chapter we describe alchemical methods allowing the calculation of relative free energy differences. We concentrate on the binding free energies that can be obtained using non-equilibrium approaches based on the Crooks Fluctuation Theorem. Together with the theoretical background, the chapter covers practical aspects of hybrid topology generation, simulation setup, and free energy estimation. An important aspect of the validation of a simulation setup is illustrated by means of calculating free energy differences along a full thermodynamic cycle. We provide a number of examples, including protein–ligand and protein–protein binding as well as ligand solvation free energy calculations.

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Notes

  1. 1.

    Distance restraints on the P α , P γ and the Mg+2 will keep the atoms in their respective orientation in one of the two top clusters shown in Fig. 12b.

  2. 2.

    A shorter transition time of 200 ps also gave a result that was fairly close to zero, but longer times were used to reduce the error.

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Authors and Affiliations

  1. Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

    Vytautas Gapsys, Servaas Michielssens, Jan Henning Peters, Bert L. de Groot & Hadas Leonov

Authors
  1. Vytautas Gapsys
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  2. Servaas Michielssens
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  3. Jan Henning Peters
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  4. Bert L. de Groot
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  5. Hadas Leonov
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Corresponding author

Correspondence to Bert L. de Groot .

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Editors and Affiliations

  1. University of Hertfordshire, Hatfield, Hertfordshire, United Kingdom

    Andreas Kukol

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Gapsys, V., Michielssens, S., Peters, J.H., de Groot, B.L., Leonov, H. (2015). Calculation of Binding Free Energies. In: Kukol, A. (eds) Molecular Modeling of Proteins. Methods in Molecular Biology, vol 1215. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1465-4_9

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  • DOI: https://doi.org/10.1007/978-1-4939-1465-4_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1464-7

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