Analysis of the binding modes and resistance mechanism of four methyl benzimidazole carbamates inhibitors fungicides with Monilinia fructicola β2-tubulin protein

•Analysis of the mechanism of saction of wild-type and mutant Monilinia fructicola beta-tubulin protein resistance.•Ligand docking predicts cross resistance to MBCs fungicides for the E198A, E198Q, F200Y.•Study of the free energy of interacting amino acid residues. Monilinia fructicola can infest plants during fruit flowering and during fruit storage and transportation, causing serious economic losses. The resistance problem of methyl benzimidazole carbamates inhibitors fungicide is becoming more and more prominent as the use time increases. By exploring the molecular binding mode, we studied the changes of the binding mode of the main amino acid residues between the four MBCs fungicides and the wild type and mutant Monilinia fructicoloa beta-tubulin protein constructed by homologous modeling. Constructing homology related models through sequence alignment based on sequence information from Monilinia fructicola beta-tubulin protein. Molecular docking and molecular dynamics simulations were then used to identify the optimum binding mode of benomyl, carbendazim, thiabendazole and thiophanate-methyl with Monilinia fructicola beta-tubulin protein. Furthermore, we calculated the binding free energy of four wild-type and mutant protein-ligand complexes using MM/PBSA. The result shows that when E198A was mutated, the hydrogen bonding force of thiophanate-methyl binding to the protein was reduced. The possible underlying cause of the resistance is the disappearance of the π-π stacking interaction with Phe200. When E198Q was mutated, all three fungicides, excluding carbendazim, interacted with Gln198 of the protein through hydrogen bonding. However, the binding pattern of carbendazim, thiophanate-methyl were least affected. When F200Y was mutated, the binding pocket of benomyl is slightly altered concerning the binding pattern between the wild-type protein and the fungicide concerning the amino acid residues. The resistance mechanism of M. fructicola beta-tubulin protein to MBCs fungicides and the mechanism of cross-resistance between MBCs fungicides were initially elucidated by computer simulation. [Display omitted]