A COMPUTER MODELING STUDY OF HYDROGEN-BONDS IN LIGAND-BETA-ADRENOCEPTOR COMPLEXES - ITS IMPLICATIONS IN THE DEDUCTION OF A RECEPTOR MAP

Recent experimental evidence indicates that the side chain carboxylate group of an aspartic acid residue located at position 113 (Asp113) in the pharmacologically important β-adrenergic receptor protein is directly involved in the binding of β-adrenergics, most of which are analogues of phenylethanolamines or phenoxypropanolamines. The binding species is known to be the aminic monocation. This has led to the hypothesis that a direct interaction takes place between the carboxylate group at the receptor and the protonated amino function of the ligand. In the present study, a quantum-mechanical conformational analysis of the ethanolamine-formate complex is presented. This work has enabled us to construct a β-adrenoceptor map which accounts for the binding of some major classes of β-adrenergic ligands. The results of this study suggest that hydrogen bonding plays a role in the interaction between these ligands and the β-adrenoceptor. © 1990.