Targeting Amide Herbicides by KARI of Staphylococcus aureus- an in silico Analysis

Background: Herbicides are classified either by toxicity or by mechanism of action, based on the chemical nature of the compound. Herbicides fall into two categories. Contact the herbicide and the transferred herbicide. Herbicides have been selected because they are highly toxic to plants and less toxic to animals and humans, but the main concern is the direct toxic effects of herbicides on animals. Since ketol acid reductoisomerase (KARI) is considered an acceptable target for most amide herbicides, this study conducted an in-silico analysis of KARI from Staphylococcus aureus against eight amide herbicides, obsessed with investigating by performing virtual molgro molecule docking. Materials and Methods: The ilvC gene encoding KARI from Staphylococcus aureus was amplified and its sequence and chimera were checked using the GenBank project`s CHIMERA CHECK program. It uses the BLAST algorithm and the GenBank database to compare the environment sequence with the GenBank sequence to find evolutionary relatives. Homology modeling of Staphylococcus aureus ketol acid reductoisomerase (KARI) was performed because its three-dimensional structure revealed by either X-ray crystallography or NMR studies was not available. The generated model was used to repeat the energy minimization cycle many times using SPDBV software, and the final model was also used to perform docking analysis against the amide herbicide used in the inhibitor study. Results: The amplified DNA fragment containing 1005 base sequence BLAST hit, shows an absolute open reading frame encoding the Staphylococcus aureus protein KARI. PROSITE method shows active site residues Gln28, Leu79, Leu80, Asp82, Ala106, His107, Pro129, Lys130, Gly131, Pro132, Glu186, Asp190, Glu194, Cys199. The alignment of the protein sequence Ketol acid reductoisomerase (KARI) from Staphylococcus aureus and template >1NP3A had a chain length of 327. The three-dimensional structure of Staphylococcus aureus ketol acid reductoisomerase (KARI) was predicted using SPDBV. The generated model used SPDBV software to repeatedly repeat the energy minimization cycle, so the final model received a stereochemical evaluation. After energy minimization, the energy of the protein model is 1.10 KJ / mol, which fits the Ramachandran diagram. Docking studies of Staphylococcus aureus ketol acid reductoisomerase (KARI) were initiated using the inhibitors reported in the literature. This model was then used to dock to various ligands, amides that act as herbicides. In silico models have demonstrated that this enzyme is effective against amide herbicides. Conclusion: On the idea of the docking scores, these ligands (amide herbicides) were assigned the results of favorable interactions between the compounds, and therefore the situation of KARI to search out more impregnable candidates out of the screened ligands, optimization of those amides should be extended further.

Automated summary

The study conducted virtual molecular docking of KARI from Staphylococcus aureus with eight amide herbicides, demonstrating the enzyme's effectiveness against these herbicides. The results suggest potential for optimizing these amides as stronger candidates for herbicide development.