Molecular Characterization Of AVM And IVM That Bind To GABA Receptor

The avermectins (AVMs) were widely used in agriculture since it had highefficiency, low toxicity and no residue and other excellent characteristics. The use ofAVM complied with low carbon life and the trend of green chemistry. But as AVMapplication prolonged, insects produced resistance to it, which leading to the pesticideless effective. Due to this phenomenon, scientists had to constantly design newpesticide to substitute the primary. However, the AVM insecticidal mechanism waspoorly studied in molecular level. Based on this, three kinds of insect’s GABA receptor(house fly GABA receptor, Drosophila melanogaster RDL receptor and Drosophilamelanogaster multiple receptor) were built by homology modeling. According to theRamachandran plot, far more than90%of the residues in all these GABAR modelswere either in the most accepted or in the additionally accepted regions.As some papers showed, AVM located in the transmembrane domain at theinterface between two subunits near the exocellular area. At last AVM/IVM weredocked to three kinds of GABA receptor before and after mutations with Surflex-Docksoftware. The results showed that the binding free energy of AVM/IVM with GABAreceptors (house fly GABA receptor, Drosophila melanogaster RDL receptor andDrosophila melanogaster multiple receptor) were-7.84Kcal/moL and-4.75Kcal/moLrespectively, which indicated that AVM had more bond strength than IVM. This wasconsistent with the experimental results and the fact that AVM had higher toxic.However, compared with the primary receptors the binding free energy of AVM/IVMafter mutation were0.31~3.59Kcal/moL higher. This demonstrated that mutationalinsect’s GABA receptors had less affinity to AVM/IVM, this may explain that genemutations lead to Insect Resistance.