Chemoinformatics and pharmacoinformatics approach for exploring the GABA-A agonist from Chinese herb suanzaoren

This study is the first one to construct the reliable structure of the alpha 1/gamma 2 interface of Gamma aminobutyric acid type A (GABA-A) receptor by homology modeling and refined every loop of the whole protein structure. The modeling GABA-A receptor was validated by docking the control compounds in binding site, checking the key residue in alpha 1/gamma 2 interface, probability density function (PDF) value, and Ramachandran plot. This paper is also the first one to propose that jujubogenin is the effective component in suanzaoren decoction, neither jujuboside A nor jujuboside B by chemoinformatics and pharmacoinformatics approach. In addition, pharmacophore analysis showed that the oxygens on jujubogenin approached alpha 1-TYR160 and gamma 2-LYS184, respectively. The comparative molecular field analysis (CoMFA) model yielded a q(cv)(2) value of 0.731 and an r(2) of 0.942 at 5 components. Comparative molecular similarity indices analysis (CoMSIA) produced a q(cv)(2) of 0.617 and an r(2) of 0.921 at 5 components. The CoMFA and CoMSIA models showed statistically significant results. Hence, based on the results of docking, ADMET descriptor, pharmacophore, and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies, the jujubogenin was suggested to be the effective GABA-A agonist in suanzaoren decoction. (c) 2008 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.