title: Pseudoreceptor models and 3D-QSAR for imidazobenzodiazepines at GABA A/BzR subtypes alphaxbeta3gamma2 [x = 1-3, 5, and 6] via flexible atom receptor model.
abstract: Since benzodiazepines have been used widely in the treatment of anxiety, sleeplessness, and epilepsy, the receptor sites for the benzodiazepine are of prime importance. Quantitative structure-activity relationship (QSAR) studies and receptor modeling via Flexible Atom Receptor Model (FLARM) for the binding affinities of a series of imidazobenzodiazepines at five recombinant receptor subtypes were carried out successfully. The 3D-QSAR models for all five receptor subtypes were examined by a set of test set and demonstrated their high predictability for affinities of imidazobenzodiazepines at five receptor subtypes. The pseudoreceptors yielded by FLARM were compared to the united pharmacophore/receptor model. The result shows that two hydrogen bonds and other regions in the united pharmacophore/receptor model are presented in the pseudoreceptors, which demonstrates the receptor modeling capability of FLARM. The models and pseudoreceptors can help design high affinity ligands on the GABA(A)/BZ receptor and understand the GABA(A) receptor.
authors.affiliation: Institute of Process Engineering, Chinese Academy of Sciences, P.O. Box 353, Beijing 100080, People's Republic of China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Lu
authors.forename: Jiaju
authors.initials: J
authors.lastname: Zhou
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000737:chemistry*
chemical_list: D011963:Receptors, GABA-A; D001569:Benzodiazepines