Pleotropic potential of quorum sensing mediated N-acyl homoserine lactones (AHLs) at the LasR and RhlR receptors of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen, having complicated quorum sensing (QS) system utilizing multiple signals and receptors to coordinate virulence pathogenicity. N-acyl-homoserine-lactones (AHLs) are the most common autoinducers responsible for regulation of QS-mediated gene expression. There four QS systems in P. among which LasI/R RhlI/R regulated by 3-oxo-C12-HSL C4-HSL respectively. They play a major role host-associated pathogenesis. The LasR RhlR binding specificity cognate or non-cognate HSLs influences responses. Here, we used computational approaches consolidate interaction different types produced with receptors. To explore affinity, fourteen AHLs were subjected molecular docking analysis was modelled using MMseqs2 ColabFold: Alpha fold 2. Further, validate stability mechanism, dynamic simulations performed top docked six 100 ns. In results, apart from C4-HSL, other such as C16-HSL C6-HSL showed better affinity towards proteins, Further validation that 3-oxo-C10-HSL 3-oxo-C6-HSL formed stable complex RhlR, Our comprehensive silico study results may provide promising targets development anti-QS drugs against Las/Rhl systems.