Homology Modeling Of Caenorhabditis Elegans And Zebraosh γ-aminobutyric Acid Receptor And Molecular Docking

The γ-aminobutyric acid receptor （GABAR） is ligand-gated ion channel complex andis widely distributed in central nervous system, which is one of the important targets ofdrugs. So GABA receptor, especially GABA_Areceptor, is a hot spot for development ofdrugs in related fields. In this paper, three-dimensional structures of Caenorhabditiselegans and zebrafish GABA_Areceptors were obtained by homology modeling,Furthermore, the molecular docking to explore the mechanism of fipronil and IBIPPSbinding with Caenorhabditis elegans and GABA_Areceptor. Fipronil and its derivativeswere docked into the putative binding site of zebrafish GABA_Areceptor model bySurflex-docking and analysised the results, the results showed the important group and ofzebrafish GABA_Areceptor.First, using the caenorhabditis elegans glutamic acid receptor （PDB ID:3RHW,3.6）as a template, caenorhabidtis elegans and zebrafish GABA_Areceptor were generated byhomology modeling. Both of dynamics simulation and conformational analyses indicatedthat two receptors were reasonable.Second, In order to explore the mechanism of Fipronil and IBIPPS binding withCaenorhabditis elegans GABA_Areceptor, Fipronil and IBIPPS were docked into theputative binding site of Caenorhabditis elegans GABA_Areceptor model bySurflex-docking,and the results showed that Thr45and Thr49of TM2play an importantrole in ligand binding of the Caenorhabditis elegans GABA_Areceptor. Surflex-dockinganalys show that fipronil and IBIPPS fitted into the putative binding pockets located in thecytopl asmic half of TM2, and IBIPPS has higher potency toward Caenorhabditis elegansGABA_AR than fipronil toward Caenorhabditis elegans GABA_AR.Third, forty six fipronil and its derivatives were docked into zebrafish GABA_Areceptor,found that benzene ring were replaced by CF₃, Cl and pyrazole ring were replaced bySOCF₃or SO₂CF₃respectively, compounds had toxicity on zebrafish.Fourth, I defined similar to80%of fipronil to search the compounds in the NCI-2000datebase. The result showed that25compounds fitted the query. After these compoundswere docked into the zebrafish GABA_Areceptor and the result verified the third research conclusion. The results of Fipronil docking with zebeafish GABA_Areceptor showed thatASN28and ARG38of TM2play an important role in ligand binding of the zebrafishGABA_Areceptor.