Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008.

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TitleCommunity-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008.
Publication TypeJournal Article
Year of Publication2009
AuthorsMichino, M, Abola, E, Brooks, CL, J Dixon, S, Moult, J, Stevens, RC
Corporate AuthorsGPCR Dock 2008 participants
JournalNat Rev Drug Discov
Volume8
Issue6
Pagination455-63
Date Published2009 Jun
ISSN1474-1784
KeywordsAnimals, Crystallization, Crystallography, X-Ray, Drug Design, Drug Industry, Humans, Ligands, Models, Molecular, Predictive Value of Tests, Protein Binding, Receptor, Adenosine A2A, Receptors, G-Protein-Coupled, Structure-Activity Relationship, Triazines, Triazoles
Abstract

Recent breakthroughs in the determination of the crystal structures of G protein-coupled receptors (GPCRs) have provided new opportunities for structure-based drug design strategies targeting this protein family. With the aim of evaluating the current status of GPCR structure prediction and ligand docking, a community-wide, blind prediction assessment - GPCR Dock 2008 - was conducted in coordination with the publication of the crystal structure of the human adenosine A(2A) receptor bound to the ligand ZM241385. Twenty-nine groups submitted 206 structural models before the release of the experimental structure, which were evaluated for the accuracy of the ligand binding mode and the overall receptor model compared with the crystal structure. This analysis highlights important aspects for success and future development, such as accurate modelling of structurally divergent regions and use of additional biochemical insight such as disulphide bridges in the extracellular loops.

DOI10.1038/nrd2877
Alternate JournalNat Rev Drug Discov
PubMed ID19461661
PubMed Central IDPMC2728591
Grant ListF30 DE017522-04 / DE / NIDCR NIH HHS / United States
P41 RR012255 / RR / NCRR NIH HHS / United States
P50 GM073197 / GM / NIGMS NIH HHS / United States
P50 GM073197-05 / GM / NIGMS NIH HHS / United States
U54 GM074961 / GM / NIGMS NIH HHS / United States
U54 GM074961 / GM / NIGMS NIH HHS / United States
U54 GM074961-040001 / GM / NIGMS NIH HHS / United States