Computational analysis of mutated AHAS in response to sulfonylurea herbicides

Abstract

SummarySulfonylurea (SU) herbicides that target acetohydroxyacid synthase (AHAS, also called acetolactate synthase (ALS)) are regarded as one of the most important classes of herbicides, due to their extremely low toxicity towards mammals, ultra‐low dosage application and high selectivity. However, mutations of AHAS to a herbicide‐insensitive form appear to be a worldwide problem for acquired resistance. In this study, three mutated AHAS sequences were used. In the mutated AHASs, the proline (Pro) was replaced by one of threonine (Thr), alanine (Ala) or serine (Ser) in AHAS amino acid (AA) position 197Pro. To understand the herbicide resistance mechanism, we built dimeric AHAS complex models based on 1YBH of protein data bank (PDB) with SU herbicide, chlorimuron ethyl (CIE), using a homology. The three mutated AHASs in complex with CIE were analysed, and the resistance mechanism to SU herbicides was studied by molecular dynamics (MD) simulation performed using GROMACS 4.5.5. MD simulation analysis of wild‐type and the three mutated dimeric AHAS–CIE complex systems revealed the conformational stability and changes in herbicide binding to dimeric AHAS system due to the mutation. Additionally, it showed that conformational change of amino acid residue 200Met (methionine) was associated with the imidazolinone herbicide resistance mechanism. According to our computation, the detailed mechanism of herbicide resistance was variable, depending on the type of mutated amino acid, providing new insights for designing herbicides specific to each mutant AHAS.