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

doi:10.1007/978-1-4939-7465-8_4

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

Research output: Chapter in Book / Report / Conference proceeding › Chapter › Academic › peer-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.

Original language	English
Title of host publication	Computational Methods for GPCR Drug Discovery
Editors	Alexander Heifetz
Place of Publication	New York, NY
Publisher	Humana Press Inc
Pages	73-113
Number of pages	41
ISBN (Electronic)	9781493974658
ISBN (Print)	9781493974641, 9781493984947
DOIs	https://doi.org/10.1007/978-1-4939-7465-8_4
Publication status	Published - 2018

Publication series

Name	Methods in Molecular Biology
Publisher	Humana Press
Volume	1705
ISSN (Print)	1064-3745
ISSN (Electronic)	1940-6029

Funding

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.

Funders	Funder number
European Cooperation in Science and Technology	CM1207
Københavns Universitet

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1007/978-1-4939-7465-8_4

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title = "A Structural Framework for GPCR Chemogenomics: What{\textquoteright}s In a Residue Number?",

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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doi = "10.1007/978-1-4939-7465-8\_4",

language = "English",

isbn = "9781493974641",

series = "Methods in Molecular Biology",

publisher = "Humana Press Inc",

pages = "73--113",

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}

A Structural Framework for GPCR Chemogenomics: What’s In a Residue Number? / Vass, Márton; Kooistra, Albert J.; Verhoeven, Stefan et al.
Computational Methods for GPCR Drug Discovery. ed. / Alexander Heifetz. New York, NY: Humana Press Inc, 2018. p. 73-113 (Methods in Molecular Biology; Vol. 1705).

Research output: Chapter in Book / Report / Conference proceeding › Chapter › Academic › peer-review

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AU - Verhoeven, Stefan

AU - Gloriam, David

AU - de Esch, Iwan J.P.

AU - de Graaf, Chris

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KW - Chemogenomics

KW - Crystal structures

KW - Drug discovery

KW - G protein-coupled receptors

KW - GPCRs

KW - Ligand repurposing

KW - Mutations

KW - Numbering schemes

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

Abstract

Publication series

Funding

UN SDGs

Keywords

Access to Document

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