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
Part of the Methods in Molecular Biology book series (MIMB, volume 1705)


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.

Key words

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



Netherlands eScience Center/NWO (3D-e-Chem, grant 027.014.201, to C.d.G). M. V., A. J. K., D. G., I. J. P. d. E. and C. d. G. participate in the COST Action CM1207 (GLISTEN). M. V., D. G., and C. d. G. participate in the GPCR Consortium (gpcrconsortium.org). Vignir Isberg and Christian Munk (GPCRdb (http://gpcrdb.org), University of Copenhagen) are acknowledged for useful discussions on the developments of the GPCRdb KNIME nodes.


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Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  • Márton Vass
    • 1
  • Albert J. Kooistra
    • 1
    • 2
  • Stefan Verhoeven
    • 3
  • David Gloriam
    • 4
  • Iwan J. P. de Esch
    • 1
  • Chris de Graaf
    • 1
  1. 1.Department of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and SystemsVrije Universiteit AmsterdamAmsterdamThe Netherlands
  2. 2.Centre for Molecular and Biomolecular Informatics (CMBI)Radboud University Medical CenterNijmegenThe Netherlands
  3. 3.Netherlands eScience CenterAmsterdamThe Netherlands
  4. 4.Department of Drug Design and PharmacologyUniversity of CopenhagenCopenhagenDenmark

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