Three-dimensional models for agonist and antagonist complexes with beta 2 adrenergic receptor.
Computer-modeling techniques have been used to generate docked complexes for a series of beta adrenergic agonists and antagonists with a three-dimensional model of the beta 2 adrenergic receptor. For all ligands tested, it proved possible to dock low-energy conformers in the receptor model, with sensible electrostatic, steric, and hydrogen-bonding interactions, many of which are supported by experimental studies of the beta 2 receptor. Our results illustrate the power of molecular modeling techniques, when coupled with appropriate experimental methods and data, to investigate structure-function properties of integral membrane receptor proteins that cannot yet be studied by direct structural methods.
Kontoyianni
M
M
Molecular Bioengineering Program, University of Washington, Seattle 98195-1750, USA.
DeWeese
C
C
Penzotti
J E
JE
Lybrand
T P
TP
D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D006224:Cricetinae; D004837:Epinephrine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011412:Propanolamines / Q000737:chemistry / Q000378:metabolism; D011433:Propranolol / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013141:Spiro Compounds / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D014422:Turkeys
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D013141:Spiro Compounds; C014382:carazolol; C050894:spirendolol; D011433:Propranolol; D004837:Epinephrine