Subtractive genomic approach to uncover novel drug targets in Salmonella typhimurium and computational screening of food-based polyphenols as inhibitors

Introduction: and screen food-based polyphenols as potential inhibitors. Methods: A subtractive genomics approach was used to identify essential, pathogen-specific proteins. A lead target was prioritized based on its druggability, localization, and network interactions. The target's 3D structure was then modeled for molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations with a polyphenol library. Results: The screening identified UDP-N-acetylglucosamine transferase (MurG) as a promising and previously unexplored drug target. The polyphenol 6-prenylnaringenin showed a superior binding affinity for MurG compared to the antibiotic ciprofloxacin. Subsequent MD simulations and binding free energy calculations confirmed that the MurG-6-prenylnaringenin complex was significantly more stable. Conclusion: findings.