Predicting compounds that interact with the 2 known agonist-induced conformations of the human β1-adrenoceptor.

ABSTRACT: The β1-adrenoceptor exists in at least 2 agonist-stabilized conformational ensembles: a "catecholamine" ensemble induced via the intrahelical binding site through which catecholamines and most agonists act and a "secondary" ensemble of conformations through which CGP12177 stimulates agonist responses. Several β-ligands stimulate agonist responses through both conformations, resulting in biphasic concentration responses, but little is known about the structure-activity relationship of such ligands. Using a structure-activity hypothesis built on the predicted poses CGP12177 and 3 biphasic agonists (alprenolol, oxprenolol, and bucindolol), predictions based on ligand similarity and structural compatibility reasoning were made about 11 other β1-ligands not yet tested for secondary conformation

SUBMITTER: Baker JG 

PROVIDER: S-EPMC12799587 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature