The Molecular Dynamic Simulation of Zolpidem Interaction with Gamma Aminobutyric Acid Type A Receptor

Abstract

Our goal was to generate the extracellular domain of gamma-aminobutyric acid type A receptor (GABA A receptor) by comparative modeling and to study the interaction of zolpidem with the GABA A receptor. The modeling strategy was verified to provide reasonable 3-dimensional coordinates. These coordinates helped to combine all the subunits well. The benzodiazepine (BZ) binding site was located in a binding pocket between the a1 and g2 subunits of the GABA A receptor. Zolpidem was selected to dock into the binding site. In our study, the residues of the binding pocket were suggested to be aHis129, aTyr187, aGly228, aThr234, aTyr237, gMet96, gPhe116, gSer130, gGly143, and gMet169. By the calculation of the docking module, the conformation of zolpidem docking in the BZ binding site was investigated. A hydrogen bond was found at gArg136 when zolpidem's conformation was in rank 2 of the docking score. The contracted binding pocket showed residues at aHis129, aTyr187, aGly228, aTyr237, gPhe116, and gMet169. Zolpidem docking in a contracted binding pocket might generate a hydrogen bond in aHis129.

Insights into the suanzaoren mechanism—From constructing the 3D structure of GABA-A receptor to its binding interaction analysis

“…Unfortunately, the structural analysis of membrane-bound proteins through X-ray crystallography or a spectroscopic technique is not easy because of the rapid protein denaturation at the time of extraction from the physiological membrane environment. As a result of lacking a valid GABA-A receptor structure, acetylcholine bindingprotein (AChBP, Protein Data Bank ID: 1I9B) was employed as the template to simulate the GABA-A receptor structure (Brejc et al, 2001;Chen, 2007;Chen and Chen, 2007a;Ci et al, 2007;Ernst et al, 2003;Sancar et al, 2007). The three-dimensional structure obtained via structural bioinformatics (Chou, 2004a) for a targeted protein can provide us a footing or starting point for drug design in a timely manner; hence, significantly expedite its development pace.…”

“…Molecular modeling and CADD, a rapid raising technique including comprehensive physical chemistry and computer science, are important methods in modern high-throughput drug design. Docking studies have been used for investigating ligand-receptor interaction and revealing the binding mechanism (Chen, 2007(Chen, , 2008aChen and Chen, 2007a,b,c;Chen et al, 2008a,b;Chou, 2004a,b;Chou et al, 2003Chou et al, , 2006Du et al, 2005aDu et al, ,b, 2007Gao et al, 2007;Guo et al, 2008;Li et al, 2007a,b;Wang et al, 2007aWang et al, ,b,c, 2008Wei et al, 2005Wei et al, , 2006aWei et al, ,b, 2007Zhang et al, 2006;Zheng et al, 2007;Zhou and Troy, 2005a,b). Several scoring functions including piecewise linear potential (PLP), potential of mean force (PMF), and dockscore are employed to estimate ligand binding affinity (Gehlhaar et al, 1995;Muegge and Martin, 1999;Venkatachalam et al, 2003).…”

Magnolol encapsulated by different acyl chain length of liposomes on inhibiting proliferation of smooth muscle cells

“…Chemical engineering technology has been penetrating all fields of modern biotechnology, especially nanotechnology, pharmacoinformatics, membrane technology, and computer-aided drug design (Chen, 2007(Chen, , 2008aChen et al, 2008a,b;Chu et al, 2007;Lin et al, 2007a,b;Liou et al, 2008;Liu and Chen, 2007;Tao et al, 2008;Ting et al, 2008;Wang and Liu, 2008;Wu et al, 2007Wu et al, , 2008Yang et al, 2008;You et al, 2008;Zhou et al, 2008). In this study, the traditional Chinese herb, magnolol, was modified by different acyl chain lengths liposome.…”

Discovery of novel inhibitors for c-Met by virtual screening and pharmacophore analysis

“…Even if these compounds were proved to efficiently inhibit c-Met by biological experiment, the clinical administration of these compounds still exist numerous doubts such as undesired side effect. The docking study and structurebased drug design were employed for the analysis of the protein structure and drug development (Chen, 2007(Chen, , 2008aChen, 2007a,b, 2008;Chen et al, 2008a,b). In addition, the structure-based drug design gives insight into discovering potent inhibitors with fewer side effects.…”