Investigating Aromadendrin Role as a Potential Inhibitor of Acyl-Homoserine Lactone Synthase through Molecular Docking and Dynamics

Background: The widespread use of antibiotics to combat bacterial infections has led to the alarming rise of antibiotic resistance and the development of biofilms, both of which exacerbate disease severity and mortality rates. Biofilms, structured communities of bacteria, rely heavily on quorum sensing (QS)—a communication system that bacteria use to regulate collective behavior. This process is mediated by chemical signaling molecules known as autoinducers. Interrupting the production of these molecules, specifically by targeting key enzymes like acyl-homoserine lactone synthase (AHL synthase), could significantly boost antibiotic effectiveness and inhibit biofilm development. In this context, aromadendrin, a type of flavanonol in the flavonoid family, known for its wide-ranging medicinal benefits, is investigated for its capacity to inhibit AHL synthase activity.Methods: To evaluate the interaction and binding affinity of aromadendrin with AHL synthase, molecular docking techniques were performed using AutoDock ۴.۲.۲ software. Molecular dynamics (MD) simulations were employed utilizing the AMBER۹۹SB force field and were executed within the GROMACS ۲۰۱۹.۶ platform. The study performed in Ghalib Bioinformatics Center, Kabul. Afghianitan in ۲۰۲۴.Results: The results from molecular docking and MD simulations demonstrated strong hydrogen bonding and van der Waals interactions with binding energy of -۶.۷۸ (KCal/mol) between aromadendrin and AHL synthase. These interactions highlight aromadendrin's potential as a promising inhibitor analog targeting AHL synthase.Conclusion: By impeding bacterial communication pathways, aromadendrin can potentially diminish biofilm formation and enhance antibiotics' therapeutic impact, offering a novel and valuable approach to addressing antibiotic resistance and bacterial resilience.Background: The widespread use of antibiotics to combat bacterial infections has led to the alarming rise of antibiotic resistance and the development of biofilms, both of which exacerbate disease severity and mortality rates. Biofilms, structured communities of bacteria, rely heavily on quorum sensing (QS)—a communication system that bacteria use to regulate collective behavior. This process is mediated by chemical signaling molecules known as autoinducers. Interrupting the production of these molecules, specifically by targeting key enzymes like acyl-homoserine lactone synthase (AHL synthase), could significantly boost antibiotic effectiveness and inhibit biofilm development. In this context, aromadendrin, a type of flavanonol in the flavonoid family, known for its wide-ranging medicinal benefits, is investigated for its capacity to inhibit AHL synthase activity. Methods: To evaluate the interaction and binding affinity of aromadendrin with AHL synthase, molecular docking techniques were performed using AutoDock ۴.۲.۲ software. Molecular dynamics (MD) simulations were employed utilizing the AMBER۹۹SB force field and were executed within the GROMACS ۲۰۱۹.۶ platform. The study performed in Ghalib Bioinformatics Center, Kabul. Afghianitan in ۲۰۲۴. Results: The results from molecular docking and MD simulations demonstrated strong hydrogen bonding and van der Waals interactions with binding energy of -۶.۷۸ (KCal/mol) between aromadendrin and AHL synthase. These interactions highlight aromadendrin's potential as a promising inhibitor analog targeting AHL synthase. Conclusion: By impeding bacterial communication pathways, aromadendrin can potentially diminish biofilm formation and enhance antibiotics' therapeutic impact, offering a novel and valuable approach to addressing antibiotic resistance and bacterial resilience.

کلیدواژه ها:

Acyl-homoserine lactones synthase ، Aromadendrin ، Molecular docking ، Molecular dynamic simulation