Molecular docking-based screening of methicillin-resistant Staphylococcus aureus FEM proteins with FDA-approved drugs

Area of Science:

• Microbiology and Infectious Diseases
• Drug Discovery and Development
• Computational Chemistry

Background:

• Antibiotic resistance represents a critical global public health crisis.
• Folic acid and Methanol (FEM) proteins are essential for bacterial cell wall biosynthesis, specifically the pentaglycine cross-bridge formation in peptidoglycan.
• Due to their necessity for bacterial survival and role in antibiotic resistance, FEM proteins are attractive targets for novel antibacterial agents.

Purpose of the Study:

• To identify potential inhibitors of FEM proteins using virtual screening.
• To evaluate FDA-approved drugs and structurally similar molecules for their ability to inhibit FEM proteins.
• To analyze the inhibitory affinity and pharmacokinetic properties (ADMET) of selected drug candidates.

Main Methods:

• Virtual screening of a library of FDA-approved drugs and their analogs.
• In silico analysis of inhibitory affinity against FEM proteins.
• Assessment of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties for pharmacokinetic profiling.

Main Results:

• Successful identification and selection of several FDA-approved drugs and related molecules demonstrating potential as FEM protein inhibitors.
• Quantitative analysis of binding affinity and predicted pharmacokinetic profiles for the identified compounds.
• The study provides a data-driven foundation for further development of FEM protein-targeting antimicrobials.

Conclusions:

• Virtual screening effectively identified existing drugs and novel analogs with potential to inhibit FEM proteins.
• The selected compounds exhibit promising inhibitory affinity and favorable ADMET properties, warranting further investigation.
• This research lays the groundwork for designing innovative antimicrobial therapies to combat antibiotic resistance.