Selectivity of Imidacloprid for fruit fly versus rat nicotinic acetylcholine receptors by molecular modeling.
For better understanding of the mechanisms of selective binding of the representative nicotinic acetylcholine receptor (nAChR) agonist neonicotinoid Imidacloprid (IMI), three-dimensional models of fruit fly alpha 1 beta 2 and rat alpha 4beta 2 nAChRs were generated by homology modeling, using the crystal structure of the acetylcholine-binding protein (AChBP) of Lymnaea stagnalis and the nAChR of mus musculus as the templates, respectively. The conformational stability of the two models was studied by molecular dynamics (MD) and the quality of the models was confirmed. Especially, insecticide Imidacloprid was docked into the putative binding site of the fruit fly alpha 1 beta 2 and rat alpha 4 beta 2 nAChRs by Surflex-docking. The calculated docking energies were in agreement with the experimental data and the putative binding sites were also consistent with the results from labeling and mutagenesis experiments. Furthermore, the mechanisms of Imidacloprid selectively acting on fruit fly versus rat nAChRs were discussed.
Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430073, People's Republic of China.
Gen-Yan
GY
Liu
Xiu-Lian
XL
Ju
Jin
J
Cheng
D000109:Acetylcholine / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008195:Lymnaea / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D000073943:Neonicotinoids; D018722:Nicotinic Agonists / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009574:Nitro Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D018722:Nicotinic Agonists; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; C082359:imidacloprid; D000109:Acetylcholine