Computational Screening of Streptomyces Polyketides Targeting GyrB in Staphylococcus aureus : Docking and Molecular Dynamics

ABSTRACT

In silico analyses were conducted to investigate the interactions between Streptomyces‐derived polyketides and GyrB of methicillin‐resistant Staphylococcus aureus (MRSA). Among the tested compounds, 1‐hydroxy‐1‐norresistomycin exhibited the most favorable predicted docking score (XP score: −6.236 kcal/mol), while rapamycin showed a less favorable score (−3.360 kcal/mol). To assess the structural and dynamic behavior of the complexes, 100 ns molecular dynamics (MD) simulations were performed for 1‐hydroxy‐1‐norresistomycin and the reference ligand B48. The averaged RMSD, RMSF, R _g , and SASA values indicated comparable dynamic behavior between both complexes, with minimal backbone deviations (0.099 nm vs. 0.098 nm). Slight local fluctuations observed for 1‐hydroxy‐1‐norresistomycin may reflect conformational adjustments within the binding pocket without substantially affecting the overall structural characteristics of the protein. Overall, the molecular dynamics results suggest that both 1‐hydroxy‐1‐norresistomycin and the reference ligand B48 exhibited comparable dynamic behavior with the target protein during the 100 ns simulation, as reflected by their similar RMSD, RMSF, R _g , and SASA values. The differences between the complexes were minimal, suggesting that the overall structural characteristics and compactness of the protein were maintained under the simulated conditions. Therefore, HNM showed favorable predicted interactions and dynamic behavior comparable to B48, supporting its consideration as a candidate for further experimental investigation.