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A Hybrid Virtual Screening Protocol Based on Binding Mode Similarity

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Rational Drug Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1824))

Abstract

In structure-based virtual screening (SBVS), a scoring function is usually applied to rank a database of docked compounds. Docking programs are often successful in reproducing experimental binding modes; however, the estimation of binding affinity still is the Achilles’ heel of docking. The integration of SB and ligand-based (LB) methods is considered a promising strategy to increase hit rates in VS. Herein, we describe a hybrid protocol that is based on the assessment of binding mode similarity between docked compounds and a bound reference ligand. In this context, both experimental and computationally modeled poses have been successfully used as references for three-dimensional (3D) similarity calculations. In this chapter, the methods applied in recent validation studies are described.

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Acknowledgment

We thank OpenEye Scientific Software, Inc., for a free academic license of the OpenEye Toolkit and Chemical Computing Group, Inc., for academic teaching licenses of the Molecular Operating Environment.

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Authors and Affiliations

  1. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany

    Andrew Anighoro & Jürgen Bajorath

Authors
  1. Andrew Anighoro
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  2. Jürgen Bajorath
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Corresponding author

Correspondence to Jürgen Bajorath .

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Editors and Affiliations

  1. Division of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece

    Thomas Mavromoustakos

  2. Division of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece

    Tahsin F. Kellici

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Anighoro, A., Bajorath, J. (2018). A Hybrid Virtual Screening Protocol Based on Binding Mode Similarity. In: Mavromoustakos, T., Kellici, T. (eds) Rational Drug Design. Methods in Molecular Biology, vol 1824. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8630-9_9

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  • DOI: https://doi.org/10.1007/978-1-4939-8630-9_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8629-3

  • Online ISBN: 978-1-4939-8630-9

  • eBook Packages: Springer Protocols

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