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Computational Drug Discovery and Design pp 487–499Cite as

Free Energy Calculations from One-Step Perturbations

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 819))

Abstract

The one-step perturbation approach offers an efficient means to estimate free energy differences. It may be applied to estimate solvation free energies, conformational preferences or relative free energies of binding of series of compounds to a common receptor. Applicability of the method depends on the possibility to define a proper reference state which may in itself be an unphysical molecule. Here, we describe practical considerations and explicit guidelines to define a proper reference state, and to efficiently calculate relative free energies. The strengths and limitations of the method are highlighted and special considerations are noted. The method may be applied using many different simulation programs. Here, analyses are exemplified at the hand of the GROMOS simulation package.

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Authors and Affiliations

  1. Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Vienna, Austria

    Chris Oostenbrink

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  1. Chris Oostenbrink
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Correspondence to Chris Oostenbrink .

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Editors and Affiliations

  1. University of Utah, 30 South 2000 East Rm 307, Salt Lake City, 84112-5820, California, USA

    Riccardo Baron

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Oostenbrink, C. (2012). Free Energy Calculations from One-Step Perturbations. In: Baron, R. (eds) Computational Drug Discovery and Design. Methods in Molecular Biology, vol 819. Springer, New York, NY. https://doi.org/10.1007/978-1-61779-465-0_28

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  • DOI: https://doi.org/10.1007/978-1-61779-465-0_28

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-61779-464-3

  • Online ISBN: 978-1-61779-465-0

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