Binding modes of acetolactate synthase with nicosulfuron in Amaranthus retroflexus L. and potential resistance sites prediction

In order to study the resistance mechanism of Amaranthus retroflexus L. to acetolactate synthase (ALS) inhibitor, homologous modeling was conducted to construct the three-dimensional structure of ALS based on its amino acid sequence of Amaranthus retroflexus L.. Molecular docking and molecular dynamics simulations were used to predict the binding mode between the ALS of Amaranthus retroflexus L. and nicosulfuron. Based on the binding mode, analysis of the resistance reason at the reported mutations of Pro 197, Trp 574 and other sites indicated the existence of important hydrophobic interactions, π-π interactions and other interactions between the residues of the above site and nicosulfuron, or special structures of the residues that affected the channel shape. Analysis shows that non-covalent interactions between the ALS and nicosulfuron, such as hydrogen bonding and hydrophobic interactions, and changes in the channels shape might affect the binding stability and cause the weeds resistance. These results predicted that the mutations at Val 196, Met 200, Phe 206 and Lys 256 might also change the sensitivity of weeds to ALS inhibitors. In this study, the ALS resistance mechanism was analyzed using computer simulation techniques, and the results provided a reference for the design of anti-resistant herbicides.