Homology model-assisted elucidation of binding sites in GPCRs

Anat Levit, Dov Barak, Maik Behrens, Wolfgang Meyerhof, Masha Y. Niv*

*Corresponding author for this work

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

41 Scopus citations


G protein-coupled receptors (GPCRs) are important mediators of cell signaling and a major family of drug targets. Despite recent breakthroughs, experimental elucidation of GPCR structures remains a formidable challenge. Homology modeling of 3D structures of GPCRs provides a practical tool for elucidating the structural determinants governing the interactions of these important receptors with their ligands. The working model of the binding site can then be used for virtual screening of additional ligands that may fit this site, for determining and comparing specificity profiles of related receptors, and for structure-based design of agonists and antagonists. The current review presents the protocol and enumerates the steps for modeling and validating the residues involved in ligand binding. The main stages include (a) modeling the receptor structure using an automated fragment-based approach, (b) predicting potential binding pockets, (c) docking known binders, (d) analyzing predicted interactions and comparing with positions that have been shown to bind ligands in other receptors, (e) validating the structural model by mutagenesis.

Original languageAmerican English
Title of host publicationMembrane Protein Structure and Dynamics
Subtitle of host publicationMethods and Protocols
PublisherHumana Press Inc.
Number of pages27
ISBN (Print)9781627030229
StatePublished - 2012

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745


  • Agonist
  • Antagonist
  • Binding site
  • Broad tuning
  • Docking
  • GPCR model
  • Molecular recognition
  • Receptor range
  • Taste receptors


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