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Ligand-Binding Calculations with Metadynamics

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Book cover Biomolecular Simulations

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2022))

Abstract

All-atom molecular dynamics simulations can capture the dynamic degrees of freedom that characterize molecular recognition, the knowledge of which constitutes the cornerstone of rational approaches to drug design and optimization. In particular, enhanced sampling algorithms, such as metadynamics, are powerful tools to dramatically reduce the computational cost required for a mechanistic description of the binding process. Here, we describe the essential details characterizing these simulation strategies, focusing on the critical step of identifying suitable reaction coordinates, as well as on the different analysis algorithms to estimate binding affinity and residence times. We conclude with a survey of published applications that provides explicit examples of successful simulations for several targets.

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Acknowledgements

The author wishes to thank Kristen Marino, Sebastian Schneider, and Abhijeet Kapoor for the critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Davide Provasi

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  1. Davide Provasi
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Correspondence to Davide Provasi .

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Editors and Affiliations

  1. Structural Bioinformatics Unit, Institut Pasteur, CNRS UMR 3528, Paris, France

    Massimiliano Bonomi

  2. Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy

    Carlo Camilloni

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Provasi, D. (2019). Ligand-Binding Calculations with Metadynamics. In: Bonomi, M., Camilloni, C. (eds) Biomolecular Simulations. Methods in Molecular Biology, vol 2022. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9608-7_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9608-7_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9607-0

  • Online ISBN: 978-1-4939-9608-7

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