Experimental and computational correlation and prediction on herbicide resistance for acetohydroxyac

• 作 者: HE YinWu NIU CongWei LI Hank WEN Xin XI Zhen
• 机 构: State Key Laboratory of Elemento-Organic Chemistry,Department of Chemical Biology,Nankai University,
• 出 处: Science China(Chemistry)
• 发表日期: 2013年03期
• 关键词: QSAR CoMFA mutation unified transformed steric alignment contour favorable minim

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 herbicide 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 measured.The 3D-QSAR method has been transformed to process the AHAS mutants and proposed as mutation-dependent biomacromolecular QSAR(MB-QSAR).The excellent correlation between experimental and computational data gave the MB-QSAR/CoMFA model(q2=0.615,r2=0.921,r2 pred=0.598) and the MB-QSAR/CoMSIA model(q2=0.446,r2=0.929,r2 pred=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.