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论文类型：期刊论文

发表时间：2012-06-01

发表刊物：JOURNAL OF MOLECULAR MODELING

收录刊物：SCIE

卷号：18

期号：6

页面范围：2279-2289

ISSN号：1610-2940

关键字：Nicotinic acetylcholine receptor; Neonicotinoid; 3D-QSAR; Mutation; MD simulation; Molecular docking

摘要：Nicotinic acetylcholine receptor (nAChR) is a target for insect-selective neonicotinoid insecticides (NNs), exemplified by imidacloprid (IMI). In the present study, 78 IMI derivatives reported as inhibitors of Drosophila melanogaster nAChR (Dm-nAChR) and Musca domestica nAChR (Md-nAChR) were used for three-dimensional quantitative structure-activity relationship (3D-QSAR) studies. Two optimal models with good predictive power were obtained: Q (2) = 0.64, R (2) (pred) = 0.72 for Dm-nAChR, and Q (2) = 0.63, R (2) (pred) = 0.62 for Md-nAChR. In addition, homology modeling, molecular dynamic (MD) simulation, and molecular docking also showed that amino acids located within loops A, C, D and E play key roles in the interaction of Dm-/Md-nAChR with NNs. This is highly consistent with the results of graphical analysis of 3D-QSAR contour plots. Mutation analysis also implicates the Y/S mutation within loop B as being associated closely with NN resistance in Drosophila and Musca. The results obtained lead to a better understanding not only of interactions between these antagonists and Dm-/Md-nAChR, but also of the essential features that should be considered when designing novel inhibitors with desired activities.