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Computational Methods for GPCR Drug Discovery pp 73–113Cite as

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

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

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HV, Amsterdam, The Netherlands

    Márton Vass, Albert J. Kooistra, Iwan J. P. de Esch & Chris de Graaf

  2. Centre for Molecular and Biomolecular Informatics (CMBI), Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands

    Albert J. Kooistra

  3. Netherlands eScience Center, 1098 XG, Amsterdam, The Netherlands

    Stefan Verhoeven

  4. Department of Drug Design and Pharmacology, University of Copenhagen, 2100, Copenhagen, Denmark

    David Gloriam

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  1. Márton Vass
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  2. Albert J. Kooistra
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  3. Stefan Verhoeven
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  4. David Gloriam
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  5. Iwan J. P. de Esch
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  6. Chris de Graaf
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Correspondence to Chris de Graaf .

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  1. Evotec (UK) Ltd., Abingdon, Oxfordshire, United Kingdom

    Alexander Heifetz

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Vass, M., Kooistra, A.J., Verhoeven, S., Gloriam, D., de Esch, I.J.P., de Graaf, C. (2018). A Structural Framework for GPCR Chemogenomics: What’s In a Residue Number?. In: Heifetz, A. (eds) Computational Methods for GPCR Drug Discovery. Methods in Molecular Biology, vol 1705. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7465-8_4

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  • DOI: https://doi.org/10.1007/978-1-4939-7465-8_4

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