Fipronil, which block GABAA receptor choloride channels, was a successful insecticide for crop protection and public hygiene. It showed high toxicity on fishes, indicated a high affinity against both insect and fish GABAA receptors. Better understanding the potential differential actions of fipronil on these two receptor species, might be helpful in finding selective insecticides with low fish toxicity. By homology modeling method, the structures of fruitfly RDL and zebrafish �3 GABAA receptors were constructed based on the structure of GluCl channel (PDB ID: 3RHW). Then, docking and molecular dynamics simulation studies were performed to explore the binding features of fipronil with these two GABAA receptors. During 30ns molecular dynamics simulation, fipronil was found erecting in both channels, and blocked normal pass of chloride ions. The binding of fipronil with zebrafish GABAA receptor was observed more close to the extracellular part than the binding in fruitfly GABAA receptor. The simulation results well illustrated key roles of residues 2'Ala, 6'Thr and 9'Leu of the TM2 domain, which had been found in previous experimental studies. Also, 5'Ile was revealed as key residue responsible for the potential difference between the binding modes of fipronil with fruitfly and zebrafish GABAA receptors. These results might be helpful in designing selective insecticides against insect GABAA receptors.

Binding difference of fipronil with fruitfly and zebrafish GABA<sub>A</sub> receptors: Homology modeling, docking, and molecular dynamic simulation studies

248th National Meeting (2014)

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Binding difference of fipronil with fruitfly and zebrafish GABAA receptors: Homology modeling, docking, and molecular dynamic simulation studies

Binding difference of fipronil with fruitfly and zebrafish GABA_A receptors: Homology modeling, docking, and molecular dynamic simulation studies