Homology Modeling Of Honeybee And Peach-potato Aphid Nicotinic Acetylcholine Receptor With Docking Of Neonicotinoids

Nicotinic acetylcholine receptor (nAChR) belongs to ligand-gated ion channels(LGICs), which mediate the fast actions of neurotransmitters at synapses invertebrate and insect nervous systems. The structure and function of insect nAChRsare poorly studied compared to their vertebrate counterparts, which are importantbinding targets for neonicotinoids. To gain a better understanding of the interactionmechanisms of insecticide IMI with honeybee (Apis mellifera) and peach-potatoaphid (Myzus persicae) nAChRs, and to develop a novel neonicotinoid which isselectively toxic to Myzus Persicae and safe to Apis Mellifera, the computer-aideddrug design was used. Three-dimensional models of honeybee α1/β1andpeach-potato aphid α2/β1nicotinic acetylcholine receptors (nAChR) were generatedby homology modeling, using the crystal structure of the acetylcholine-bindingprotein of Lymnaea stagnalis as the template, and the quality of the models wasconformed by Ramachandran map, molecular dynamics and RMSF map. nAChRagonist Imidacloprid (IMI) was docked with the honeybee α1/β1and peach-potatoaphid α2/β1nAChRs by Surflex-docking, respectively. The calculated dockingenergies were in agreement with the experimental data. The docking resultsdemonstrate that even though both of Cscore values are high, the bindingmechanisms are quite different. The nitro group of IMI plays a key role fornon-selectivity between the honeybee and peach-potato aphid nAChRs, whichclarified that the use of IMI was high risk to the honeybee population. Then, othersix neonicotinoids were docked into the putative binding site of two nAChRs, All ofthem had high Cscores for binding to peach-potato aphid α2/β1nAChR. Forhoneybee α1/β1nAChR, the interaction of acetamiprid, thiacloprid and dinotefuranwere weaker compared with nitenpyram, clothianidin and thiacloprid.