title: CH/π hydrogen bonds play a role in ligand recognition and equilibrium between active and inactive states of the β2 adrenergic receptor: an ab initio fragment molecular orbital (FMO) study.
abstract: We examined CH/π hydrogen bonds using an ab initio fragment molecular orbital (FMO) method, combined with the CHPI program, to evaluate complexes of active (bound with agonist 1) and inactive (bound with inverse agonist 2) β2 adrenergic receptor (β(2)AR) states. In both states, we found that CH/π hydrogen bonds were present. Subtle changes in the binding pocket between the active and inactive states of β(2)AR were observed. Comparison of the CH/π networks in both states suggests that the networks differ at the β(2)AR core. Recombination of the CH/π hydrogen bonds occurred during conversion between the two states. We suggest that CH/π hydrogen bonds play a key role in ligand recognition and conversion between the active and inactive states.
authors.affiliation: Kissei Pharmaceutical Company Ltd, Central Research Laboratory, Hotaka, Azumino-City, Nagano-Pref., Japan. tomonaga_ozawa@pharm.kissei.co.jp
authors.forename: Tomonaga
authors.initials: T
authors.lastname: Ozawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Okazaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitaura
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000737:chemistry; D054314:Drug Inverse Agonism; D006860:Hydrogen Bonding; D008024:Ligands; D008968:Molecular Conformation; D011412:Propanolamines / Q000737:chemistry; D011485:Protein Binding; D011789:Quantum Theory; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D008024:Ligands; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C014382:carazolol