Molecular Drug Resistance Prediction for Acetohydroxyacid Synthase Mutants Against Chlorsulfuron Using MB-QSAR  

作　　者：Yinwu He Congwei Niu Xin Wen Zhen Xi 

机构地区：[1]State Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, Nankai University, Tianjin 300071, China

出　　处：《Chinese Journal of Chemistry》2013年第9期1171-1180,共10页中国化学（英文版）

基　　金：This work was financially supported by MOST，the National Natural Science Foundation of China

摘　　要：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.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.

关 键 词：MB-QSAR QSAR drug resistance prediction acetohydroxyacid synthase CHLORSULFURON 

分 类 号：S511[农业科学—作物学] P618.130.2[天文地球—矿床学]