草地贪夜蛾鱼尼丁受体与双酰胺类杀虫剂的结合模式及抗性风险分析

为研究草地贪夜蛾Spodoptera frugiperda (以下简称FAW) 对双酰胺类杀虫剂的抗性机制，根据FAW鱼尼丁受体 (ranodine receptor，RyR) 跨膜区域的氨基酸序列，通过同源建模的方法构建其三维结构；通过对比FAW与小菜蛾Plutella xylostella (以下简称DBM)RyR跨膜区域的氨基酸序列，发现两者具有较高的同源度，进而根据已报道的FAWRyR的突变位点I4734M及DBMRyR的突变位点G4946E (对应FAWRyR的G4891)，在FAWRyR中引入突变，采用分子对接的方法分别分析其突变前后与5种双酰胺类杀虫剂的结合模式。结果表明:FAWRyR的I4734M突变模型与5种双酰胺类杀虫剂的亲和力与野生型的无明显差别，均存在氢键、卤键、疏水作用、π-π相互作用及π-阳离子作用等非共价相互作用；但G4891E突变模型与5种双酰胺类杀虫剂的亲和力下降、形成的作用力方式减少，从而影响RyR与双酰胺类杀虫剂的结合稳定性。本研究分析发现，FAWRyR的G4891E突变可能导致其对双酰胺类杀虫剂产生抗性，需在今后的研究中关注该突变。该研究结果还可会为基于鱼尼丁受体设计杀虫剂提供参考。

Analysis of binding modes and resistance risk between ryanodine receptor of Spodoptera frugiperda and diamide insecticides

To study the resistance mechanism of Spodoptera frugiperda (FAW) to diamide insecticides, the three-dimensional structure of the transmembrane region of FAWRyR was constructed by homologous modeling based on its amino acid sequence in this work. It was found those two had high homology degree compared with the amino acid sequence of FAW and Plutella xylostella (DBM) RyR. In addition, the mutation was introduced into the model of FAWRyR according to the reported mutation site of FAWRyR (I4734M) and DBMRyR mutation site G4946E (corresponding to G4891 in FAWRyR), and the binding modes between the wild-type (WT) & mutant FAWRyRs and five kinds of diamides were analyzed by molecular docking. The binding affinity between the substitutions I4734M and diamides showed no significant difference, compared with that between WT FAWRyR and diamides. Both the substitution I4734M and WT FAWRyR existed important non-covalent interactions, such as hydrogen bond, halogen bond, hydrophobic interaction, π-stacking and π-cation interaction. However, the substitution G4891E produced reduction in binding affinity and the number of action mode, which affected the binding stability of FAWRyR and diamides. These results indicated that the substitution G4891E could cause the resistance of FAWRyR to diamides. And future research should focus on the G4891E mutation of FAWRyR. Moreover, this reserch could provide a reference for RyR-structure-based insecticides design.