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

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

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.

LanguageEnglish
Title of host publicationComputational Methods for GPCR Drug Discovery
EditorsAlexander Heifetz
PublisherHumana Press Inc
Pages73-113
Number of pages41
ISBN (Electronic)9781493974658
ISBN (Print)9781493974641
DOIs
Publication statusPublished - 2018

Publication series

NameMethods in Molecular Biology
Volume1705
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Fingerprint

G-Protein-Coupled Receptors
Binding Sites
Ligands
Workflow
Mutation

Keywords

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

Cite this

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 A. Heifetz (Ed.), Computational Methods for GPCR Drug Discovery (pp. 73-113). (Methods in Molecular Biology; Vol. 1705). Humana Press Inc. https://doi.org/10.1007/978-1-4939-7465-8_4
Vass, Márton ; Kooistra, Albert J. ; Verhoeven, Stefan ; Gloriam, David ; de Esch, Iwan J.P. ; de Graaf, Chris. / A Structural Framework for GPCR Chemogenomics : What’s In a Residue Number?. Computational Methods for GPCR Drug Discovery. editor / Alexander Heifetz. Humana Press Inc, 2018. pp. 73-113 (Methods in Molecular Biology).
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Vass, M, Kooistra, AJ, Verhoeven, S, Gloriam, D, de Esch, IJP & de Graaf, C 2018, A Structural Framework for GPCR Chemogenomics: What’s In a Residue Number? in A Heifetz (ed.), Computational Methods for GPCR Drug Discovery. Methods in Molecular Biology, vol. 1705, Humana Press Inc, pp. 73-113. https://doi.org/10.1007/978-1-4939-7465-8_4

A Structural Framework for GPCR Chemogenomics : What’s In a Residue Number? / Vass, Márton; Kooistra, Albert J.; Verhoeven, Stefan; Gloriam, David; de Esch, Iwan J.P.; de Graaf, Chris.

Computational Methods for GPCR Drug Discovery. ed. / Alexander Heifetz. Humana Press Inc, 2018. p. 73-113 (Methods in Molecular Biology; Vol. 1705).

Research output: Chapter in Book / Report / Conference proceedingChapterAcademicpeer-review

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Vass M, Kooistra AJ, Verhoeven S, Gloriam D, de Esch IJP, de Graaf C. A Structural Framework for GPCR Chemogenomics: What’s In a Residue Number? In Heifetz A, editor, Computational Methods for GPCR Drug Discovery. Humana Press Inc. 2018. p. 73-113. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-7465-8_4