Study of molecular mechanisms of herbicide binding t o target proteins of weeds by in silico methods

Abstract

The aim of this study was to study of the molecular mechanisms of herbicide binding (pinoxaden, quizalofop- P-tephuryl, prometryn, metribuzin, metsulfuron- methyl) to target proteins (acetyl- CoA carboxylase, acetolactate synthase, cytochrome P450, p-hydroxyphenylpyruvate dioxygenase) of the weed species growing in Siberia: wild oat Avena fatua (L.), wheatgrass Elymus repens (L.), amaranth Amaranthus retro exus (L.), common lamb's quarters Chenopodium album (L.), bristlegrass Setaria viridis (L.). The work was carried out in the Novosibirsk region in 2022-2023. Using bioinformatic methods, virtual three- dimensional complexes of pesticides and their targets were created. A new approach has been proposed to identify the parameters of the cavity of binding sites, which consists in combining the alignment method and machine learning technology. Docking of pesticides with targets was carried out. The calculation of the binding energy indicates a high degree of stability of the ligand- protein complexes. The in silico approach we proposed may be useful for elucidating the behavior of herbicides when bound to weed enzymes. This approach allows a deeper understanding of the mechanism of action and ecotoxicological aspects of the use of pesticides. The studied complexes of herbicides and proteins have a potential high stability due to the low binding energy with receptors, which varies from -5.60 to -13.24 kcal/mol. The binding energy value did not show a direct dependence on the number of amino acid residues of the ligand- binding site. In general, the study supplemented some aspects of the molecular mechanisms of binding herbicides to target proteins of weeds, however, a more in-depth study is required in order to localize critical amino acid points involved in the biological functions of target proteins.