Structure‐Based Virtual Screening of Propolis‐Derived Compounds as Quorum Sensing Inhibitors in <i>Stenotrophomonas maltophilia</i> Using Molecular Docking and Dynamics Simulations

Abstract

ABSTRACT Multidrug resistance (MDR) represents a major global health concern, particularly in opportunistic pathogens such as Stenotrophomonas maltophilia , whose virulence, biofilm formation, and antimicrobial resistance are partly regulated by quorum sensing (QS). We employed an in silico structure‐based screening method to identify QS inhibitors from Moroccan propolis that interact with the RPFC receptor which functions as a crucial element in the diffusible signal factor (DSF) signaling pathway. We assessed a collection of 106 propolis‐derived compounds by applying Lipinski's rules and ADMET profiling to identify 30 candidates who possessed drug‐like characteristics. The molecular docking studies demonstrated that, kaempferol, acetyl flavone, and cedeodarin exhibited binding affinities to RPFC which exceeded the interaction strength of the natural ligand DSF. The 100 nanosecond molecular dynamics simulations established that the RPFC‐ligand complexes maintained structural integrity throughout the simulation and kaempferol exhibited the most secure and ongoing interactions while acetyl flavone and cedeodarin displayed stable binding patterns. The study demonstrates that Moroccan propolis contains bioactive compounds which function as QS inhibitors and can be used to develop novel strategies for managing S. maltophilia biofilm formation and antimicrobial resistance. The therapeutic potential needs confirmation through additional testing which should include both in vitro and in vivo research.