Dror et al. used computational modelling to garner information on how ligands bind to the allosteric binding site on G protein-coupled receptors (GPCRs). The authors determined conformations of the M2 muscarinic acetylcholine receptor in combination with several structurally diverse allosteric ligands, which revealed they had similar binding interactions — some of which were contrary to previous predictions. This information was then used to make structural changes to ligands to alter their predicted allosteric effects in in vitro studies.
References
Dror, R. O. et al. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs. Nature 503, 295–299 (2013)
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Harrison, C. Structural insights into allosteric GPCR drugs. Nat Rev Drug Discov 12, 906 (2013). https://doi.org/10.1038/nrd4188
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DOI: https://doi.org/10.1038/nrd4188