分子动力学模拟设计方法是药物辅助设计的有效方法之一。研究表明，当抑制剂分子(配体)与其抗性ALS分子(受体)结构对接时，配体与受体对接复合分子构象的均方根偏差（RMSD）振幅大,出现双峰分布态,RMSD值和对接构象旋转半径（Rg）轨迹的二维图呈现不稳态的双团分布态，结合自由能值相对大；而与感性ALS对接时，上述指标参数值相反。本项目研究目的在于前期对ALS第197位抗药突变型表现高亲和力的磺酰脲类化合物设计基础上，进一步设计对ALS第574位和653位抗药突变型具有高亲和力的磺酰脲类除草剂新结构，通过实物合成及其除草活性特征的鉴定，论证在分子动力学除草剂模拟设计中，不同抑制剂（配体）与靶标（受体）对接分子构象的RMSD和Rg指标参数差异特征的真实性和新结构黄酰脲类化合物合成工艺的可行性，为反抗药性ALS抑制剂的研发提供新的分子结构设计原理和方法，并提供新型反抗类除草剂品种结构。

The method of molecular dynamics simulation was used to design for herbicidal structure. Previous studies show there were significant differences in the root mean square deviation (RMSD), the radius of gyration (Rg) and the Gibbs binding free energy between wild type and mutant ALS-chlorimuron ethyl (CIE) binding conformations. The distribution for the wild type formed a single cluster and the binding free energy is larger, but those for the mutated types were scattered to form more than two noticeable clusters and the binding free energy is smaller. The additional clusters for the mutants were located at a higher RMSD and Rg compared with the cluster for the wild type. Based on previous works conducted by project team, new sulfonylurea structures with smaller RMSD, Rg and binding free energy were designed. And these new structures show high affinity and inhibitory activity for mutant ALS in theory.The aim of this study is to synthesize some new sulfonylurea herbicides with high affinity to resistant ALSs which amino acid position 574th and 653th are mutated. The new herbicides are used to identify the synthesis process and herbicidal activity. Different practical results of different parameters of RMSD and Rg on the molecular conformation of inhibitor (ligand) and target (acceptor) are verified. And this study provides new design principles and methods for the development of mutant ALS inhibitors, and provides some new sulfonylurea herbicides.