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Updated: Feb 12, 2026

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
Chemical Diversity in the G Protein-Coupled Receptor Superfamily
Márton Vass1, Albert J Kooistra1, Dehua Yang2
1Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, Amsterdam 1081 HZ, The Netherlands; M.V. and A.J.K. contributed equally to this review.
Abstract:
G protein-coupled receptors (GPCRs) are the largest family of cell signaling transmembrane proteins that can be modulated by a plethora of chemical compounds. Systematic cheminformatics analysis of structurally and pharmacologically characterized GPCR ligands shows that cocrystallized GPCR ligands cover a significant part of chemical ligand space, despite their limited number. Many GPCR ligands and substructures interact with multiple receptors, providing a basis for polypharmacological ligand design. Experimentally determined GPCR structures represent a variety of binding sites and receptor-ligand interactions that can be translated to chemically similar ligands for which structural data are lacking. This integration of structural, pharmacological, and chemical information on GPCR-ligand interactions enables the extension of the structural GPCR-ligand interactome and the structure-based design of novel modulators of GPCR function.
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