芳氧苯氧基丙酸酯类（APP）、环己二酮类（CHD）和苯基吡唑啉类（DEN）是靶向乙酰辅酶A羧化酶（ACCase）的重要的禾本科杂草除草剂。然而抗性是困扰其进一步发展的最大障碍。其中I1705L和D2004G的突变对三类除草剂均表现出了抗性。根据抑制剂在靶标中的相对位置活性腔分为：APP-活性腔和CHD-活性腔，二者相互交盖相互不同。因此本项目将基于此，采用计算机辅助药物设计的方法对活性腔进行合理地扩大---APP+CHD-活性腔，随后基于同源模建的方法构建抗性杂草看麦娘中I1705L_CT和D2004G_CT的三维结构，采用片段筛选和从头设计的方法进行新型ACCase抑制剂设计，力争通过分子设计-有机合成-生物活性测试的研究循环，获得2-3个结构新颖的、高活性、低抗性的新型ACCase抑制剂，本项目的实施将为我国新农药创制基础研究做出积极贡献。

Aryloxyphenoxypropionates (APP), cyclohexanediones (CHD), and phenylpyrazoline (DEN) targeting to acetyl-CoA carboxylase (ACCase), were used to selectively control the grass weeds in broadleaf crops. However, the resistance became the most serious problem to block them to further development. Both of I1705L and D2004G mutations showed resistance to APP, CHD, and DEN. Based on the relative location of APP and CHD in the binding target, the binding activity could be defined as APP-binding site and CHD-binding site. Most important thing was that both binding site were intertwined with each other. Therefore, we would rationally enlarge the binding site of ACCase based on both binding sites to construct the new APP+CHD-binding site by using molecular modeling method. The 3D structure of mutant type of Alopecurus aequalis (I1705L_CT and D2004G_CT) would be built using homology modeling. And then, the fragment and ab initio virtual screening would be used to design new ACCase inhibitors. We struggle to find about 2-3 lead compounds with high activity and low resistance through the design circulate. Finally, the results from this project will make a positive contribution to the basic research of new pesticides in China.