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.