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

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Abstract
To evaluate current progress in GPCR structure prediction and ligand docking, a community-wide prediction assessment — GPCR Dock 2008 — in coordination with the publication of the human adenosine A2A receptor structure in October 2008 and public release of the 3-dimensional coordinates. Twenty-nine groups submitted 206 structural models before the release of the experimental structure. The structures were evaluated for the accuracy of the ligand binding mode and the overall receptor model compared with the crystal structure. The majority of the submitted models predicted the overall topology, but did not predict the ligand position and the binding interactions very accurately. The best model overall (submitted by S. Costanzi) has a ligand RMSD of 2.8 Å RMSD and 34 of 75 correct contacts. Accurate modelling of the structurally divergent regions (such as the extracellular loops), of disulphide bond formation affecting helix residue registry and of the helical shifts in the TM region seem to be crucial for accurately predicting the key ligand interactions in GPCRs, and this area is perhaps the most in need of technological development.