有机磷和氨基甲酸酯类农药在农药市场中占据重要位置，该类农药主要作用于不同种属共有的乙酰胆碱酯酶（AChE）活性位点丝氨酸残基，因而对非靶标生物有一定的毒性。密集型农业长期过度施用农药，严重危及天敌和传粉昆虫等益虫的数量。研制选择性杀螨剂是真正高效的害螨防治策略，可以缓解螨害日益加重、非靶标生物毒性和农药抗性等问题。本研究拟采用结构建模和多重结构比对等方法，对叶螨和关键非靶标生物AChE的活性位点及周围区域进行比对分析，寻找潜在的选择性杀螨剂作用靶点。随后，从小分子化合物库、现有的农药和杀螨活性物质中，采用大规模虚拟筛选结合AChE抑制剂体外高效筛选，以及室内毒力测定和田间防效试验，筛选生物选择性好的抗AChE杀螨活性物质。采用分子对接结合结构分析和点突变验证，确定抗AChE选择性杀螨剂的作用靶点。本研究对研制新型选择性杀螨剂，有效防治害螨，具有重要的理论和实践意义。

Organophosphates and carbamates insecticides plays a key role in the world insecticide market, while these insecticides target the ubiquitous serine residue at the catalytic site of acetylcholinesterase (AChE), which cause toxicity to non-target off-species. The intensification of agriculture and increasing reliance on insecticides means that pollinators and predators are alsochronically exposed to cocktails of agrochemicals, and leads to beneficial insects declining. One effective and environmentally safe way to control spider mites is to develop new selective acaricides, which can relieve increasingly serious mite problem, and non-target off-species toxicity and insecticide resistance problems. The potential spider mite-specific AChE target will be searched through comparative structural analysis of mite and critical non-target off-species AChEs using known AChEs structures and structural models. Virtual screen combining with in vitro AChE inhibitory activity test, indoor toxicity assay and field experiment, will be used to screen selective anti-cholinesterase acaricides from small compound databases, insecticides and bioactive extracts. Molecular docking method combining with structure analysis and site mutagenesis method will be used to analyze the target of the selective AChE inhibitors, which may reveal the spider mite-specific insecticide targets. The study may enable the design of novel and safe acaricides to effectively control spider mites while sparing economically important beneficial insects.