Arthur Christopoulos

TL;DR: FITTING data with non-linear regression models as mentioned in this paper has been shown to work well with linear regression models, but not with a non-linear regression model, in the case of the CURVE.

TL;DR: Besides the heuristically interesting nature of functional selectivity, there is a clear impact on drug discovery, because this mechanism raises the possibility of selecting or designing novel ligands that differentially activate only a subset of functions of a single receptor, thereby optimizing therapeutic action.

TL;DR: There have been tremendous advances in the discovery of novel ligands for GPCRs that act at allosteric sites to regulate receptor function that provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders.

TL;DR: It is proposed that the study of allosteric phenomena will become of progressively greater import to the drug discovery process due to the advent of newer and more sensitive GPCR screening technologies.

TL;DR: The structure of an agonist-bound, active state of the human M2 muscarinic acetylcholine receptor stabilized by a G-protein mimetic camelid antibody fragment isolated by conformational selection using yeast surface display reveals larger conformational changes in the extracellular region and orthosteric binding site than observed in the active states of the β2AR and rhodopsin.