Structural Insights into Taxifolin's Potential Inhibition of AHL Synthase via Molecular Docking and Dynamics Simulations

Abstract

Background: The extensive application of antibiotics for bacterial disease treatment has resulted in the emergence of antibiotic resistance and biofilm formation, a significant issue that contributes to increased illness and death rates. Quorum sensing (QS) is cell-cell communication in bacteria involved in the formation of biofilm in which this pathway is triggered by signaling molecules called auto inducers. Inhibition of enzymes that produce such signaling molecules, for instance, acyl-homoserine lactone synthase (AHL) in QS would be appreciable to enhance the effect of antibiotics and prevent biofilm formation. Taxifolin, a subclass of flavanonols in the flavonoids, with its diverse medicinal properties was used in this study to verify the inhibition of the acyl-homoserine lactone synthase enzyme.

Methods: For finding the interaction and binding affinity between taxifolin and AHLs synthase, molecular docking was applied, using Autodock 4.2.2. MD simulations were launched to find the free enzyme and enzyme/ligand molecular structure in detail, utilizing the AMBER99SB force field within the GROMACS 2019.6 software.

Results: Outcomes from molecular docking and molecular dynamics simulations revealed favorable hydrogen bonds and van der Waals interactions between taxifolin and AHLs synthase. Using taxifolin as an inhibitor analog to target AHLs synthase showed an effective strategy against multi-drug resistance and biofilm formation.

Conclusion: We utilized computational techniques such as molecular docking and molecular dynamics simulations to propose that taxifolin, known for its diverse health benefits, could potentially inhibit AHL synthase.