title: 3D-QSAR model of flavonoids binding at benzodiazepine site in GABAA receptors.
abstract: With flavone as a structural template, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies and ab initio calculations were performed on a series of flavonoids. A reasonable pharmacophore model was built through CoMFA, CoMSIA, and HQSAR analyses and electrostatic potential calculations. A plausible binding mode for flavonoids with GABA(A) receptors was rationalized. On the basis of the commonly recognized binding site, the specific S1 and S2 subsites relating to substituent positions were proposed. The different binding affinities could be explained according to the frontier orbitals and electrostatic potential (ESP) maps. The ESP could be used as a novel starting point for designing more selective BZ-binding-site ligands.
authors.affiliation: Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, P. R. China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: T
authors.initials: T
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: R
authors.initials: R
authors.lastname: Ji
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: H
authors.initials: H
authors.lastname: Xue
authors.forename: J T
authors.initials: JT
authors.lastname: Wong
authors.forename: B L
authors.initials: BL
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Pei
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Chen
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002151:Calorimetry; D005419:Flavonoids / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity
chemical_list: D005419:Flavonoids; D008024:Ligands; D021122:Protein Subunits; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D001569:Benzodiazepines