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Exploiting Water Dynamics for Pharmacophore Screening

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Protein-Ligand Interactions and Drug Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2266))

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Abstract

Three-dimensional pharmacophore models have been proven extremely valuable in exploring novel chemical space through virtual screening. However, traditional pharmacophore-based approaches need ligand information and rely on static snapshots of highly dynamic systems. In this chapter, we describe PyRod, a novel tool to generate three-dimensional pharmacophore models based on water traces of a molecular dynamics simulation of an apo-protein.

The protocol described herein was successfully applied for the discovery of novel drug-like inhibitors of West Nile virus NS2B-NS3 protease. By using this recent example, we highlight the key steps of the generation and validation of PyRod-derived pharmacophore models and their application for virtual screening.

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Author information

Authors and Affiliations

  1. Pharmaceutical and Medicinal Chemistry, Freie Universität Berlin, Berlin, Germany

    David Schaller, Szymon Pach, Marcel Bermudez & Gerhard Wolber

Authors
  1. David Schaller
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  2. Szymon Pach
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  3. Marcel Bermudez
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  4. Gerhard Wolber
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Corresponding author

Correspondence to Gerhard Wolber .

Editor information

Editors and Affiliations

  1. Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden

    Flavio Ballante

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Schaller, D., Pach, S., Bermudez, M., Wolber, G. (2021). Exploiting Water Dynamics for Pharmacophore Screening. In: Ballante, F. (eds) Protein-Ligand Interactions and Drug Design. Methods in Molecular Biology, vol 2266. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1209-5_13

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  • DOI: https://doi.org/10.1007/978-1-0716-1209-5_13

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1208-8

  • Online ISBN: 978-1-0716-1209-5

  • eBook Packages: Springer Protocols

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