Chlorsulfuron is the first commercialized sulfonylurea herbicide, which targets acetohydroxyacid synthase （AHAS）. Mutations in AHAS have caused serious herbicide resistance to chlorsulfuron. Quantitative description...Chlorsulfuron is the first commercialized sulfonylurea herbicide, which targets acetohydroxyacid synthase （AHAS）. Mutations in AHAS have caused serious herbicide resistance to chlorsulfuron. Quantitative description of the herbicide resistance in molecular level will benefit the understanding of the resistance mechanism and aid the design of resistance-evading herbicide. We have recently established a MB-QSAR （Mutation-dependent Biomac- romolecular Quantitative Structure-Activity Relationship） method to conduct the 3D-QSAR study in biomacro- molecules. Herein, based on the herbicide resistance data measured for a series of AHAS mutants against chlorsul- furon, we constructed MB-QSAR models to quantitatively predict the herbicide resistance and interpret the struc- ture resistance relationships for AHAS mutants against chlorsulfuron. Quite well correlations between the experi- mental and the predicted pKi values were achieved for MB-QSAR/CoMFA （q^2=0.705, r^2=0.918, r^2pred=0.635） and MB-QSAR/CoMSIA （q^2=0.558, r^2=0.940, r^2pred=0.527） models, and interpretation of the MB-QSAR models gave chemical intuitive information to guide the resistance-evading herbicide design.展开更多
本工作测定了商品化除草剂阔草清对大肠杆菌乙酰羟酸合成酶Ⅱ及其突变体的抑制常数.利用生物大分子的定量构效关系方法(MB-QSAR)建立了定量、可视的突变体性质与结构关系模型.实验数据与计算数据之间显示了良好的相关性:MB-QSAR/CoMFA(c...本工作测定了商品化除草剂阔草清对大肠杆菌乙酰羟酸合成酶Ⅱ及其突变体的抑制常数.利用生物大分子的定量构效关系方法(MB-QSAR)建立了定量、可视的突变体性质与结构关系模型.实验数据与计算数据之间显示了良好的相关性:MB-QSAR/CoMFA(comparative molecular field analysis)模型的交叉验证系数q^(2)=0.691,非交叉验证相关性系数r^(2)=0.947,外部预测能力r^(2)_(pred)=0.759;MB-QSAR/CoMSIA(comparative molecular similarity indices analysis)模型的相应值分别为0.625,0.960和0.619.模型的三维结构-性质关系图为突变体抗性提供了直观阐释,为抗性规避性农药的设计提供了有价值的信息.同时,该模型也在一定程度上显示了除草剂种属选择性的预测能力.展开更多
Bispyribac is a widely used herbicide that targets the acetohydroxyacid synthase （AHAS） enzyme. Mutations in AHAS have caused serious herbicide resistance that threatened the continued use of the herbicide. So far, ...Bispyribac is a widely used herbicide that targets the acetohydroxyacid synthase （AHAS） enzyme. Mutations in AHAS have caused serious herbicide resistance that threatened the continued use of the herbicide. So far, a unified model to decipher herb- icide resistance in molecular level with good prediction is still lacking. In this paper, we have established a new QSAR method to construct a prediction model for AHAS mutation resistance to herbicide Bispyribac. A series of AHAS mutants concerned with the herbicide resistance were constructed, and the inhibitory properties of Bispyribac against these mutants were meas- ured. The 3D-QSAR method has been transformed to process the AHAS mutants and proposed as mutation-dependent biom- acromolecular QSAR （MB-QSAR）. The excellent correlation between experimental and computational data gave the MB-QSAR/CoMFA model （q2 = 0.615, P = 0.921, F2pred = 0.598） and the MB-QSAR/CoMSIA model （q2 = 0.446, r2 = 0.929, r2pred = 0.612）, which showed good prediction for the inhibition properties of Bispyribac against AHAS mutants. Such MB-QSAR models, containing the three-dimensional molecular interaction diagram, not only disclose to us for the first time the detailed three-dimensional information about the structure-resistance relationships, but may also provide further guidance to resistance mutation evolution. Also, the molecular interaction diagram derived from MB-QSAR models may aid the resistance-evading herbicide design.展开更多
基金This work was financially supported by MOST，the National Natural Science Foundation of China
文摘Chlorsulfuron is the first commercialized sulfonylurea herbicide, which targets acetohydroxyacid synthase （AHAS）. Mutations in AHAS have caused serious herbicide resistance to chlorsulfuron. Quantitative description of the herbicide resistance in molecular level will benefit the understanding of the resistance mechanism and aid the design of resistance-evading herbicide. We have recently established a MB-QSAR （Mutation-dependent Biomac- romolecular Quantitative Structure-Activity Relationship） method to conduct the 3D-QSAR study in biomacro- molecules. Herein, based on the herbicide resistance data measured for a series of AHAS mutants against chlorsul- furon, we constructed MB-QSAR models to quantitatively predict the herbicide resistance and interpret the struc- ture resistance relationships for AHAS mutants against chlorsulfuron. Quite well correlations between the experi- mental and the predicted pKi values were achieved for MB-QSAR/CoMFA （q^2=0.705, r^2=0.918, r^2pred=0.635） and MB-QSAR/CoMSIA （q^2=0.558, r^2=0.940, r^2pred=0.527） models, and interpretation of the MB-QSAR models gave chemical intuitive information to guide the resistance-evading herbicide design.
文摘本工作测定了商品化除草剂阔草清对大肠杆菌乙酰羟酸合成酶Ⅱ及其突变体的抑制常数.利用生物大分子的定量构效关系方法(MB-QSAR)建立了定量、可视的突变体性质与结构关系模型.实验数据与计算数据之间显示了良好的相关性:MB-QSAR/CoMFA(comparative molecular field analysis)模型的交叉验证系数q^(2)=0.691,非交叉验证相关性系数r^(2)=0.947,外部预测能力r^(2)_(pred)=0.759;MB-QSAR/CoMSIA(comparative molecular similarity indices analysis)模型的相应值分别为0.625,0.960和0.619.模型的三维结构-性质关系图为突变体抗性提供了直观阐释,为抗性规避性农药的设计提供了有价值的信息.同时,该模型也在一定程度上显示了除草剂种属选择性的预测能力.
文摘Bispyribac is a widely used herbicide that targets the acetohydroxyacid synthase （AHAS） enzyme. Mutations in AHAS have caused serious herbicide resistance that threatened the continued use of the herbicide. So far, a unified model to decipher herb- icide resistance in molecular level with good prediction is still lacking. In this paper, we have established a new QSAR method to construct a prediction model for AHAS mutation resistance to herbicide Bispyribac. A series of AHAS mutants concerned with the herbicide resistance were constructed, and the inhibitory properties of Bispyribac against these mutants were meas- ured. The 3D-QSAR method has been transformed to process the AHAS mutants and proposed as mutation-dependent biom- acromolecular QSAR （MB-QSAR）. The excellent correlation between experimental and computational data gave the MB-QSAR/CoMFA model （q2 = 0.615, P = 0.921, F2pred = 0.598） and the MB-QSAR/CoMSIA model （q2 = 0.446, r2 = 0.929, r2pred = 0.612）, which showed good prediction for the inhibition properties of Bispyribac against AHAS mutants. Such MB-QSAR models, containing the three-dimensional molecular interaction diagram, not only disclose to us for the first time the detailed three-dimensional information about the structure-resistance relationships, but may also provide further guidance to resistance mutation evolution. Also, the molecular interaction diagram derived from MB-QSAR models may aid the resistance-evading herbicide design.
