Integrating molecular docking and molecular dynamics simulation studies of afzelechin as a potential inhibitor of Acyl-homoserine lactones (AHLs) synthase

Abstract

Introduction: The random usage of antimicrobial agent and inadequate beneficial approaches leads to recurrent   relapse of infection due to microorganism resistance. These obstacles have led to the development of multi-drug resistance (MDR) and, as a result, the formation of biofilms. Acyl-homoserine lactones are signaling molecules involved in Quorum sensing (QS) has been studied for its role in propagating resistance, thus causing the establishment of a stable microbial population. The Acyl-homoserine lactones (AHLs) synthase inhibitors agents can be used to suppress the QS and acts as an agent against biofilm formation. Finding natural derivatives aid in regulation and prevention of biofilm formation and exhibited promise as non-toxic agents against biofilms. afzelechin a natural compound, with multiple therapeutic effect found in Bergenia ligulata can be used as a AHLs synthase inhibitor showed by molecular docking and molecular dynamic simulation analysis. it is suggested that afzelechin could serve as potential inhibitor of AHLs synthase. Combining these natural derivatives with antibiotics could improve the mentioned outcomes.

Method: Molecular docking was utilized to investigate the interaction and binding affinity of afzelechin within the active site of AHLs synthase, employing Autodock 4.2.2 for the analysis. The configuration with the most favorable binding energy was chosen for further examination. To delve into the molecular interactions of afzelechin with AHLs synthase, MD simulations were conducted using the AMBER99SB force field within the GROMACS 2019.6 software.

Result:

The molecular docking analysis revealed that afzelechin fits appropriately within the active site of AHLs 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), 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 AHLs synthase enzyme. The results from the conducted analysis offer significant insights that could assist in the development of novel inhibitors aimed at managing biofilm formation and antibiotic resistance.