Current Computer-Aided Drug DesignCurrent Computer-Aided Drug DesignCurrent Computer-Aided Drug Design1573-40991875-6697Bentham Science64409210.2174/1573409919666230612120819ChemistryResearch ArticleIn silico Identification of Potential Inhibitors against Staphylococcus aureus Tyrosyl-tRNA SynthetaseMonobeKoheiinfo@benthamscience.netTaniguchiHinatainfo@benthamscience.netAokiShunsukeinfo@benthamscience.netDepartment of Bioscience and Bioinformatics, Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology0105202420545246207012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjeid.com/1573-4099/article/view/644092

Background:Drug-resistant Staphylococcus aureus (S. aureus) has spread from nosocomial to community-acquired infections. Novel antimicrobial drugs that are effective against resistant strains should be developed. S. aureus tyrosyl-tRNA synthetase (saTyrRS) is considered essential for bacterial survival and is an attractive target for drug screening.

Objective:The purpose of this study was to identify potential new inhibitors of saTyrRS by screening compounds in silico and evaluating them using molecular dynamics (MD) simulations.

Methods:A 3D structural library of 154,118 compounds was screened using the DOCK and GOLD docking simulations and short-time MD simulations. The selected compounds were subjected to MD simulations of a 75-ns time frame using GROMACS..

Results:Thirty compounds were selected by hierarchical docking simulations. The binding of these compounds to saTyrRS was assessed by short-time MD simulations. Two compounds with an average value of less than 0.15 nm for the ligand RMSD were ultimately selected. The longtime (75 ns) MD simulation results demonstrated that two novel compounds bound stably to saTyrRS in silico.

Conclusion:Two novel potential saTyrRS inhibitors with different skeletons were identified by in silico drug screening using MD simulations. The in vitro validation of the inhibitory effect of these compounds on enzyme activity and their antibacterial effect on drug-resistant S. aureus would be useful for developing novel antibiotics.

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