Unveiling quorum sensing mechanisms: Computational docking and dynamics of bacterial receptors and ligands

The bacterial cell-to-cell communication mechanism known as quorum sensing (QS) uses chemical cues called autoinducers (AIs) to control several processes, including pathogenicity, antibiotic resistance, and biofilm formation. This study investigates the QS receptor-ligand interactions and QS compatibility within and between bacterial species using computational molecular docking. Receptor proteins including LuxS, LuxP, AgrC, LuxN, SdiA, LasR, esaR, YenR, LamC, PlcR, and TraR were docked with their respective AIs (AHL, AI-1, AI-2, AIP1, LamD, PapR7) in both biofilm and non-biofilm producing bacteria. Our findings indicate that QS receptors exhibit high affinity for their cognate ligands, with binding affinities ≥ -4.5 Kcal/mol. Additionally, Zinc Pharmar-derived similar chemical structures demonstrated binding affinities ≥ -5.3 Kcal/mol. Density Functional Theory (DFT) analysis revealed AI-2 as the most reactive autoinducer. Molecular Dynamics (MD) simulations confirmed the stability of LasR-AHL and LuxP-AI-2 complexes. These insights pave the way for further in vitro and in vivo investigations of QS mechanisms.