Computational Analysis of LasR Inhibitors: A Novel Approach to Disrupt Quorum Sensing in Pseudomonas aeruginosa

Pseudomonas aeruginosa is a highly competitive biofilm forming bacteria that poses a significant threat to health care industries. Central to its pathogenicity is quorum sensing (QS), a cell density dependent communication system mediated by auto inducers called N-acyl homoserine lactone (AHL). To identify the potential quorum sensing inhibitors (QSI) molecular docking simulations were used to screen a library of molecules that were similar in structure to erythromycin. Top five ligands with high binding affinity to the active site of LasR were found. Further, ADMET analysis confirmed the drug likeliness of the inhibitors. Different computational analyses were carried out including the RMSF (Root Mean Square Fluctuation), RMSD (Root Mean Square Deviation), RG (Radius of Gyration), SASA (Solvent Accessible Surface Area), Inter as well as Intra Hydrogen –bonds (H- Bond), FEL (Free Energy Landscape), and MMPBSA (Molecular Mechanics/Poisson-Boltzmann Surface Area) to predict the effect of the tested QSIs on LasR. The results showed the efficacy of the two QSIs in disrupting quorum sensing mechanism in P. aeruginosa , ultimately providing insights that can be used to broaden the strategic measures to combat such bacterial infections.