Experimental and computational correlation and prediction on herbicide resistance for acetohydroxyacid synthase mutants to Bispyribac

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 (q (2) = 0.615, r (2) = 0.921, r (2) (pred) = 0.598) and the MB-QSAR/CoMSIA model (q (2) = 0.446, r (2) = 0.929, r (2) (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.