Analysis

Nature Reviews Drug Discovery 8, 455-463 (June 2009) | doi:10.1038/nrd2877

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

Mayako Michino1, Enrique Abola1, GPCR Dock 2008 participants, Charles L. Brooks, III2, J. Scott Dixon3, John Moult4 & Raymond C. Stevens5  About the authors

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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 A2A 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.

Author affiliations

  1. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
  2. Department of Chemistry and Biophysics Program, University of Michigan, Ann Arbor, Michigan 48109, USA.
  3. Daylight Chemical Information Systems Inc., Aliso Viejo, California 92656, USA.
  4. Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.
  5. Departments of Molecular Biology and Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA

Correspondence to: Raymond C. Stevens5 Email: stevens@scripps.edu

Published online 22 May 2009

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