integrating molecular docking and molecular dynamics simulation studies of afzelechin as a potential inhibitor of acyl-homoserine lactones (ahls) synthase

Introduction: misuse of antimicrobial agents and inadequate treatment methods lead to recurrent infections due to microorganism resistance, multi-drug resistance, and biofilm formation. acyl-homoserine lactones propagate resistance and establish a stable microbial population. natural derivatives like afzelechin can regulate biofilm formation and show promise as non-toxic agents against biofilms. combining these with antibiotics could improve outcomes. method: the study used molecular docking to analyze the interaction and binding affinity of afzelechin with ahl synthase, using autodock 4.2.2. the configuration with the most favorable binding energy was chosen for further study. md simulations were conducted using amber99sb force field within gromacs 2019.6 software. result: the molecular docking analysis revealed that afzelechin fits appropriately within the active site of ahl synthase, exhibiting favorable binding energy. subsequent molecular dynamics (md) simulations corroborated these findings, with evaluations of root-mean-square deviation (rmsd), root-mean-square fluctuation (rmsf), solvent-accessible surface area (sasa), and radius of gyration (rg), among other parameters, confirming the stability and suitability of the interaction. conclusion: this study reveals that afzelechin, a compound with various therapeutic properties, shows promise as an inhibitor against the ahl synthase enzyme. the results of the analysis offer significant insights that could assist in the development of novel inhibitors aimed at managing biofilm formation and antibiotic resistance.