Study Of The Interaction Between Avermectins And Glutamate Receptors

Avermectins has been recognized as a pesticide with high efficiency, low toxicityand high insect-resistant in worldwide. In recent years, due to the wide abuse of thisdrug, its potential harm like the increase of pesticide residue and drug resistance wasgradually revealed. Therefore, it is the aim of the scientists to design a high efficientbiological pesticide instead of avermectins instantly. Glutamate receptor in insects isconsidered as the target protein of avermectins. If the interaction mechanism betweenavermectins and glutamate receptor can be defined at the molecular level, the rapidconstruction of its derivatives will become true.Studies have shown that the binding affinity between avermectins and glutamatereceptors assembled with alpha or beta subunit was diverse. Based on this, the modelsof GluCl-α and GluCl-β of Caenorhabditis elegans, Haemonchus contortus andCooperia oncophora were designed with GluCl-α in C. elegans as the novel templatefor the first time. Then avermectin, ivermectin and doramectin were docked to theactive pocket of the modeled receptors respectively with Surflex-Dock software ofSYBYLX1.1. Results indicated that:(1) the free binding energy between ivermectinand GluCl-α in C. elegans was lowest (-12.06Kcal mol1), which means the highestaffinity. It is about4Kcal mol1lower than that of avermectin. It was perfectlyconsitent with the experimental conclusion that the toxicity of ivermectin is higherthan avermectin in C. elegans.(2) The free binding energy between avermectin andGluCl-α in Cooperia oncophora was-11.32Kcal mol1, which is a little higher than thatof the best. Unfortunately, there is no action between avermectin and the alpha or beta glutamate receptors in Haemonchus contortus.(3) For the beta GluCl receptors in thethree kinds of nematodes, the binding result of ivermectin is better than that ofavermectin and doramectin. In a nutshell, avermectins plays a more important role inthe reaction with GluClα than with GluClβ, and the power of toxicity for the samepestiside is different to the diverse insects with glutamate receptors assembled of thesame subunit. The conclusion was consistent with the experimental datas obtained bythe American scientists.Generally, the proportion of GluCl-α and GluCl-β in the worms is various for thedifferent regions. So the above research results can provide theoretical basis for thedesign of timely effective pesticide formulation, meanwhile for the avoidance ofenvironmental pollution and the the pharmaceutical waste.