title: Molecular dynamics simulations of m3-muscarinic receptor activation and QSAR analysis.
abstract: Molecular dynamics simulations of the rat m3-muscarinic seven-helix-bundle receptor models were performed on the free, agonist-bound and antagonist-bound forms. A comparative structural/dynamics analysis was performed in order to explain the perturbations induced by the functionally different ligands when binding to their target receptor. Theoretical quantitative structure-activity relationship models were developed; a good correlation was obtained between the interaction energies of the minimized average ligand-receptor complexes and the pharmacological affinities of the considered ligands. The consistency obtained between the structural rearrangement of the transmembrane seven-helix-bundle models considered and the experimental pharmacological efficacies and affinities of the ligands constitutes an important validation of the 3-D models proposed and allows the inference of the mechanism of ligand-induced or mutation-induced receptor activation at the molecular level.
authors.affiliation: Dipartimento di Chimica, Università di Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Fanelli
authors.forename: M C
authors.initials: MC
authors.lastname: Menziani
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
mesh_terms: D000818:Animals; D008958:Models, Molecular; D018721:Muscarinic Agonists / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic