Investigating the putative binding-mode of GABA and diazepam within GABA A receptor using molecular modeling.
The three-dimensional structure of the GABA A receptor that included the ligand/agonist binding site was constructed and validated by using molecular modeling technology. Moreover, the putative binding-mode of GABA and diazepam with GABAA receptor were investigated by means of docking studies. Based on an rmsd-tolerance of 1.0 angstroms, the docking of GABA to alpha1/beta2 interface resulted in three multi-member conformational clusters and model 2 was supported by homologous sequence alignment data and experimental evidence. On the other hand, the docking of diazepam to alpha1/gamma2 interface revealed five multi-member conformational clusters in the binding site and model 1 seemed to represent the correct orientation of diazepam in the binding site.
Ci
Suqin
S
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100080, P.R. China.
Ren
Tianrui
T
Su
Zhiguo
Z
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003975:Diazepam / Q000737:chemistry*; D018757:GABA Modulators / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011963:Receptors, GABA-A / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*