• Peptide-based antimicrobial agent against dihydrofolate reductase of Staphylococcus aureus
  • Zeynab Omidi Naegesi,1 Azizeh Asadzadeh ,2,*
    1. Department of Biology, Faculty of Basic Sciences, Royan Research Institute, Isfahan, Isfahan, Iran
    2. Department of Biology, Faculty of Basic Sciences, Nourdanesh Institute of Higher Education, Meymeh, Isfahan, Iran


  • Introduction: Staphylococcus aureus (Sa) is one of the Gram-positive pathogens that causes a wide range of clinical diseases. This pathogen can cause many different types of infections, including skin infections, bone infections, pneumonia, and endocarditis. Conversion of dihydrofolate (DHF) to tetrahydrofolate (THF) is catalyzed by dihydrofolate reductase (DHFR) in the presence of coenzyme NADPH. THF is essential in the synthesis of adenine and guanine for DNA replication. Inhibitors of dihydrofolate reductasein S. aureus leading to pathogen death. In this research, we study peptide-based antimicrobial agent against DHFR of S. aureus by in silico approach.
  • Methods: The 3D crystal structures of dihydrofolate reductase (PDB ID: 3FYV) in complex with NADPH were downloaded from the Protein Data Bank. For docking operation, by using Accelrys software, co-crystallized ligand XCF300 and all water molecules were deleted from the enzyme structure. The 3D of the peptide was designed and optimized by HyperChem Professional, and then the physical and chemical parameters of the optimized peptide were obtained by the ProtParam tool. The affinity of this peptide to dihydrofolate reductase of Staphylococcus aureus was estimated by docking operation.
  • Results: Based on the physical and chemical parameters, the designed peptide with molecular weight: 1795.36, theoretical pI: 12.02, aliphatic index: 55.71, and grand average of hydropathicity: -2.079 is a stable peptide. Our docking results showed, designed peptide with Docking Score of -194.90 binds to the binding site of 3FYV by amino acids LYS4,HIS10, HIS7 and ARG11.
  • Conclusion: Designed peptide with sequence LLKKHPHHPHRRKX while having proper stability, is able to occupy the binding site of the dihydrofolate reductase of Staphylococcus aureus, to confirm the results, experimental studies on this peptide-based antimicrobial agent are necessary.
  • Keywords: Antimicrobial Agent, Dihydrofolate reductase, Staphylococcus aureus, In silico