Community-wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008.
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.
Michino
Mayako
M
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Abola
Enrique
E
Brooks
Charles L
CL
Dixon
J Scott
JS
Moult
John
J
Stevens
Raymond C
RC
D000818:Animals; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D004345:Drug Industry / Q000379:methods; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000502:physiology; D043705:Receptor, Adenosine A2A / Q000737:chemistry* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000378:metabolism*; D014230:Triazoles / Q000378:metabolism*
D008024:Ligands; D043705:Receptor, Adenosine A2A; D043562:Receptors, G-Protein-Coupled; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385