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PMID: 16796383 Published · epublish English Journal Article Research Support, N.I.H., Extramural Review

Computational methods in drug design: modeling G protein-coupled receptor monomers, dimers, and oligomers.

The AAPS journal ·Vol. 8 ·No. 2 ·2006-05-12 ·Pages E322-36

Reggio PH

Abstract

G protein-coupled receptors (GPCRs) are membrane proteins that serve as very important links through which cellular signal transduction mechanisms are activated. Many vital physiological events such as sensory perception, immune defense, cell communication, chemotaxis, and neurotransmission are mediated by GPCRs. Not surprisingly, GPCRs are major targets for drug development today. Most modeling studies in the GPCR field have focused upon the creation of a model of a single GPCR (ie, a GPCR monomer) based upon the crystal structure of the Class A GPCR, rhodopsin. However, the emerging concept of GPCR dimerization has challenged our notions of the monomeric GPCR as functional unit. Recent work has shown not only that many GPCRs exist as homo- and heterodimers but also that GPCR oligomeric assembly may have important functional roles. This review focuses first on methodology for the creation of monomeric GPCR models. Special emphasis is given to the identification of localized regions where the structure of a GPCR may diverge from that of bovine rhodopsin. The review then focuses on GPCR dimers and oligomers and the bioinformatics methods available for identifying homo- and heterodimer interfaces.

MeSH Terms
Amino Acid Sequence Animals Dimerization Drug Design Humans Macromolecular Substances Models, Molecular Molecular Sequence Data Protein Conformation Receptor, Cannabinoid, CB1/chemistry,physiology Receptors, G-Protein-Coupled/chemistry,classification,physiology
Chemicals
Macromolecular Substances Receptor, Cannabinoid, CB1 Receptors, G-Protein-Coupled
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Reggio Patricia H
Center for Drug Design, Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, NC 27402, USA. phreggio@uncg.edu
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Article Info
Journal
The AAPS journal
Abbr.
AAPS J
ISSN
1550-7416
DOI
10.1007/BF02854903
Email
phreggio@uncg.edu
Published
2006-05-12
Epub
2006-00-12
Pages
E322-36
Language
English
Region
United States
NLM ID
101223209
PMCID
PMC3231557
Subset
IM
Grants
NIDA NIH HHS · DA00489 · United States
NIDA NIH HHS · DA03934 · United States
External Links
PubMed source DOI: 10.1007/BF02854903 PMC Full Text View journal details
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