Inhibition of Alpha-Hemolysis toxin of Staphylococcus Aureus through Molecular docking simulations

Alpha toxin, also known as α-toxin or Hla, is a potent protein toxin produced by Staphylococcus aureus. The mechanism of membrane inhibition of alpha toxin begins with the binding of the toxin monomers to specific receptors on the surface of susceptible host cells until the complex inserts into the lipid bilayer to form a transmembrane pore, resulting in cell lysis and death. We hypothesize that blocking the pore of the protein could block the pore formation on the cell surface and prevent cell lysis. The alpha toxin protein structure is obtained from the Protein Data Bank (PDB). We used AutoDock to perform the molecular docking, forecast the optimum ligand binding locations inside the protein's active site, and provide information on likely binding affinities and interactions. We used PLIP analysis to analyze and visualize protein-ligand interactions. Using our simulations, we found that Ligands III and IV exhibited the highest binding contacts with the alpha-hemolysin protein's pore-forming region due to their high binding affinities and extensive hydrophobic and hydrogen bonding interactions. The application of this study establishes the groundwork for the creation of targeted therapy treatments against Staphylococcal infections.