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Development of Optimal Virtual Screening Strategies to Identify Novel Toll-Like Receptor Ligands Using the DockBox Suite

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Toll-Like Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2700))

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Abstract

Toll-like receptors (TLRs) represent attractive targets for developing modulators for the treatment of many pathologies, including inflammation, cancer, and autoimmune diseases. Here, we describe a protocol based on the DockBox package that enables to set up and perform structure-based virtual screening in order to increase the chance of identifying novel TLR ligands from chemical libraries.

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Notes

  1. 1.

    Note that other protein preparation tools can be used like Schrödinger’s Protein Preparation Wizard [37] or the H++ server (http://newbiophysics.cs.vt.edu/H++) [38]

  2. 2.

    Free tools for compound clustering can be used for the same purpose (for example the best-first clustering scripts available at https://github.com/docking-org/ChemInfTools/tree/master/utils [24] or the diversity filtering scripts from https://www.frdr-dfdr.ca/repo/dataset/f8180e92-a7dd-4c62-b541-33282115d887 [39]).

  3. 3.

    Six pairs: Autodock-Vina, AutoDock-DOCK, AutoDock-DSX, Vina-DOCK, Vina-DSX, DOCK-DSX; four triplets: Autodock-Vina-DOCK, Autodock-Vina-DSX, Autodock-DOCK-DSX, Vina-DOCK-DSX; one quadruplet: Autodock-Vina-DOCK-DSX.

  4. 4.

    A ligand pose was assumed to be correctly predicted if, after spatial superimposition with the corresponding cocrystallized structure, RMSD over ligand atoms was lower than 2.0 Å.

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Acknowledgments

We gratefully acknowledge support from the PSMN (Pôle Scientifique de Modélisation Numérique) of the ENS de Lyon for the computing resources. F.G. was supported by a University of Ottawa start-up grant and a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant.

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Authors and Affiliations

  1. Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, Lyon, France

    Jordane Preto

  2. Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada

    Francesco Gentile

  3. Ottawa Institute of Systems Biology, Ottawa, Canada

    Francesco Gentile

Authors
  1. Jordane Preto
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  2. Francesco Gentile
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Corresponding authors

Correspondence to Jordane Preto or Francesco Gentile .

Editor information

Editors and Affiliations

  1. Department of Medicine and Surgery, University of Perugia, Perugia, Italy

    Francesca Fallarino

  2. Department of Medicine and Surgery, University of Perugia, Perugia, Italy

    Marco Gargaro

  3. Department of Medicine and Surgery, University of Perugia, Perugia, Italy

    Giorgia Manni

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Preto, J., Gentile, F. (2023). Development of Optimal Virtual Screening Strategies to Identify Novel Toll-Like Receptor Ligands Using the DockBox Suite. In: Fallarino, F., Gargaro, M., Manni, G. (eds) Toll-Like Receptors. Methods in Molecular Biology, vol 2700. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3366-3_2

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  • DOI: https://doi.org/10.1007/978-1-0716-3366-3_2

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3365-6

  • Online ISBN: 978-1-0716-3366-3

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