Potential inhibitors of FemC to combat Staphylococcus aureus: virtual screening, molecular docking, dynamics...

Area of Science:

• Microbiology
• Computational Chemistry
• Drug Discovery

Background:

• FemC is a crucial factor in methicillin resistance in *Staphylococcus aureus* (S. aureus).
• FemC influences peptidoglycan synthesis and glutamine metabolism, making it a potential drug target.
• Identifying inhibitors of FemC is vital for combating antibiotic resistance in S. aureus.

Purpose of the Study:

• To screen and identify potent antibacterial agents targeting the FemC protein.
• To evaluate the efficacy and stability of potential FemC inhibitors using computational methods.
• To provide a basis for designing novel antimicrobial scaffolds against *S. aureus*.

Main Methods:

• In silico screening of antibacterial molecules against a validated FemC model.
• Docking studies to assess binding affinity and interactions with active site residues.
• Pharmacokinetic and ADMET property evaluation.
• Molecular dynamics simulations and MMPBSA analysis to confirm complex stability and key interactions.

Main Results:

• Six candidate molecules (Z317461228, Z92241701, Z30923155, Z30202349, Z2609517102, Z92470167) were shortlisted based on docking scores and favorable properties.
• Molecular dynamics and MMPBSA analyses confirmed the stability of FemC-inhibitor complexes.
• Specific residues (S15, M16, S17, R31, R43, Q47, K48, R49) were identified as critical for stable complex formation.

Conclusions:

• The identified six molecules show significant potential as starting points for novel antimicrobial drug design.
• These compounds may lead to the development of effective treatments against *S. aureus* infections.
• The study provides a computational framework for future drug discovery efforts targeting FemC.