Exploration of the binding of DNA binding ligands to Staphylococcal DNA through QM/MM docking and molecular dynamics simulation.

DNA binding ligands (DBL) were reported to bind the minor groove of bacterial DNA. In the present study, DBL were analyzed and screened for their Staphylococcus inhibitory activity by inhibiting the Staphylococcal DNA replication. The orientation and the ligand-receptor interactions of DBL within the DNA-binding pocket were investigated applying a multi-step docking protocol using Glide and QM/MM docking. The polarization of ligands with QM/MM for DNA-ligand docking with Staphylococcal DNA minor groove was performed in order to understand their possible interactions. Molecular dynamics simulation techniques were employed to obtain the dynamic behavior of the DBL with Staphylococcal DNA. Computational docking and simulation represented a promising alternative to bridge the gap, and so that DNA and gyrase interactions were blocked by DBL. The results revealed the importance of the DBL for strong interactions with the DNA minor groove region and blocking the bacterial replication.