Exploring propolis-derived compounds as quorum sensing inhibitors for Candida albicans: a molecular docking and dynamics simulations study.

The opportunistic fungal pathogen Candida albicans (C. albicans) employs quorum sensing (QS) to regulate virulence factors such as biofilm formation and morphological switching. Targeting QS offers a promising approach to attenuate pathogenicity without promoting resistance. The objective of the present study was to computationally screen a library of 106 propolis-derived compounds to identify natural quorum-sensing inhibitors targeting the CYC and RAS1 receptors. Advanced techniques, including molecular docking, molecular dynamics (MD) simulations, and ADMET predictions, were employed to establish a workflow for structure-based virtual screening. Farnesol, used as a reference compound, showed a good binding affinity (-7.0 kcal/mol) toward CYC and RAS1 receptors. Two propolis flavonoids, kaempferol-3-O-4-O-p-coumaryl-glucoside (KCG) and isorhamnetin-3-glucoside-7-rhamnoside (IGR), exhibited stronger binding affinities with CYC and RAS1 receptors (between - 8.4 and - 10.3 kcal/mol). Based on Prime MMGBSA binding free energy calculations, the RAS1-KCG complex demonstrated the most favorable interaction, driven by significant coulombic and Van der Waals contributions. The CYC-KCG complex also showed relatively strong binding. These results highlight the potential of KCG as a versatile inhibitor capable of interacting with both targets. MD simulations further confirmed the excellent conformational stability of both KCG-receptor complexes, as indicated by low RMSD values, suggesting favorable dynamic behavior. These findings provide a strong foundation for subsequent validation.