title: A two model receptor system of the alpha1D adrenergic receptor to describe interactions with epinephrine and BMY7378.
abstract: In this study, we have developed a two receptor model system to describe the R and R states of G-protein coupled receptors, specifically the alpha(1D) adrenergic receptor. The two models interact with agonist (epinephrine) and antagonist (BMY7378) differently. The active model has increased interactions with epinephrine. The inactive model has increased interactions with BMY7378. We also explored the protonation state of the ligands. When the most basic amine was protonated, we found increased hydrogen bonding and increased aromatic interactions. Protonated epinephrine hydrogen bonds with Asp176 and has aromatic residues Trp172, Trp235, Trp361, and Phe388 within 3 Angstroms. Protonated BMY7378 hydrogen bonds with Trp172 and Lys236 and has aromatic residues Trp172, Trp254, Phe364, Phe384, and Phe388 within 3 Angstroms. We conclude that the two model system is required to represent the two states of the receptor and that protonation of the ligand is also critical.
authors.affiliation: Chemistry Department, Eastern Kentucky University, Richmond, 40475, USA. debra.bautista@eku.edu
authors.forename: Debra L
authors.initials: DL
authors.lastname: Bautista
authors.forename: Deanna H
authors.initials: DH
authors.lastname: Morris
authors.forename: Lauren
authors.initials: L
authors.lastname: Stein
authors.forename: Wesley
authors.initials: W
authors.lastname: Asher
authors.forename: Timothy
authors.initials: T
authors.lastname: Hammitt
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D004837:Epinephrine / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C053428:BMY 7378; D004837:Epinephrine