A Structural Framework for GPCR Chemogenomics: What’s In a Residue Number?

Márton Vass, Albert J. Kooistra, Stefan Verhoeven, David Gloriam, Iwan J.P. de Esch, Chris de Graaf*

*Corresponding author for this work
    4 Citations (Scopus)

    Abstract

    The recent surge of crystal structures of G protein-coupled receptors (GPCRs), as well as comprehensive collections of sequence, structural, ligand bioactivity, and mutation data, has enabled the development of integrated chemogenomics workflows for this important target family. This chapter will focus on cross-family and cross-class studies of GPCRs that have pinpointed the need for, and the implementation of, a generic numbering scheme for referring to specific structural elements of GPCRs. Sequence- and structure-based numbering schemes for different receptor classes will be introduced and the remaining caveats will be discussed. The use of these numbering schemes has facilitated many chemogenomics studies such as consensus binding site definition, binding site comparison, ligand repurposing (e.g. for orphan receptors), sequence-based pharmacophore generation for homology modeling or virtual screening, and class-wide chemogenomics studies of GPCRs.

    Original languageEnglish
    Title of host publicationMethods in Molecular Biology
    Number of pages41
    PublisherHumana Press
    Publication date1 Jan 2018
    Pages73-113
    DOIs
    Publication statusPublished - 1 Jan 2018
    SeriesMethods in Molecular Biology
    Volume1705
    ISSN1064-3745

    Keywords

    • Chemogenomics
    • Crystal structures
    • Drug discovery
    • G protein-coupled receptors
    • GPCRs
    • Ligand repurposing
    • Mutations
    • Numbering schemes

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