Journal
DRUG DISCOVERY TODAY
Volume 20, Issue 11, Pages 1355-1364Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2015.08.003
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X-ray structures of G protein-coupled receptors (GPCRs) have now been reported for more than 60 ligands and 20 receptors, including examples from GPCR classes A, B, C and F. The new structures show previously unobtainable details of interactions between GPCRs and ligands, including the roles of lipophilic regions and water molecules as key drivers of binding. In addition, the structures have revealed several surprising ligand-binding modes, including sites outside the orthosteric pocket. This new information is dramatically changing the way we approach GPCR drug discovery.
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