Three-dimensional models for agonist and antagonist complexes with beta 2 adrenergic receptor

J Med Chem. 1996 Oct 25;39(22):4406-20. doi: 10.1021/jm960241a.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Agonists / chemistry
  • Adrenergic beta-Agonists / metabolism*
  • Adrenergic beta-Antagonists / chemistry
  • Adrenergic beta-Antagonists / metabolism*
  • Amino Acid Sequence
  • Animals
  • Computer Simulation
  • Cricetinae
  • Epinephrine / chemistry
  • Epinephrine / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Propanolamines / chemistry
  • Propanolamines / metabolism
  • Propranolol / chemistry
  • Propranolol / metabolism
  • Protein Conformation
  • Rats
  • Receptors, Adrenergic, beta-2 / chemistry
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Sequence Alignment
  • Spiro Compounds / chemistry
  • Spiro Compounds / metabolism
  • Swine
  • Turkeys

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Propanolamines
  • Receptors, Adrenergic, beta-2
  • Spiro Compounds
  • carazolol
  • spirendolol
  • Propranolol
  • Epinephrine