The inhibitory mechanism of echinacoside against Staphylococcus aureus Ser/Thr phosphatase Stp1 by virtual screening and molecular modeling.

Context: Stp1 is a new potential target closely related to the pathogenicity of Staphylococcus aureus (S. aureus). In this study, effective Stp1 inhibitors were screened via virtual screening and enzyme activity experiments, and the inhibition mechanism was analyzed using molecular dynamics simulation. Methods: AutoDock Vina 4.0 software was used for virtual screening. The molecular structures of Stp1 and ligands were obtained from the RCSB Protein Data Bank and Zinc database, respectively. The molecular dynamics simulation used the Gromacs 4.5.5 software package with the Amberff99sb force field and TIP3P water model. AutoDock Tools was used to add polar hydrogen atoms to Stp1 and distribute part of the charge generated by Kollman's combined atoms. The binding free energies were calculated using the Amber 10 package. Results: The theoretical calculation results are consistent with the experimental results. We found that echinacoside (ECH) substantially inhibits the hydrolytic activity of Stp1. ECH competes with the substrate by binding to the active center of Stp1, resulting in a decrease in Stp1 activity. In addition, Met39, Gly41, Asp120, Asn162, and Ile163 were identified to play key roles in the binding of Stp1 to ECH. The benzene ring of ECH also plays an important role in complex binding. These findings provide a robust foundation for the development of innovative anti-infection drugs. [ABSTRACT FROM AUTHOR]