Molecular docking and MD simulations predicted quercetin as a potent human interleukin-1 beta (hIL1β) inhibitor for improved endodontic disease management

Abstract

IL1β, a pro-inflammatory cytokine, is a key mediator in the inflammatory processes linked to endodontic disorders. Studies have shown that IL1β production is elevated in symptomatic periapical lesions, highlighting its involvement in inflammation and lesion development. Elevated levels of IL1β correlate with larger lesion sizes and increased inflammation in periapical tissues. Given its role in inflammation, IL1β represents a potential therapeutic target for endodontic diseases, including the use of IL1β inhibitors. The present study used molecular docking and MD simulations to identify small molecule inhibitors of hIL1β. A small library of 329 plant-derived natural compounds was screened against hIL1β, the top five hits were selected based on their binding affinity and score and docked with hIL1β. Molecular docking results showed that Quercetin has the highest binding affinity (−10.3 kcal/mol) and exibits favorable interactions with hIL1β compared to the other four hits. Based on these observations, Quercetin was further subjected to MD simulations with hIL1β. MD trajectories were used to determine the interaction and stability of the hIL1β-Quercetin complex using various parameters, such as RMSD, RMSF, Rg, SASA, and hydrogen bond count of the apo hIL1β and Quercetin-hIL1β complex. Consistent RMSD, RMSF, Rg, and SASA values indicated the stability of the complex. Furthermore, hydrogen bond count emphasized the Quercetin’s role as a non-disruptive binder. Moreover, secondary structure analysis, PCA, and calculations of Gibbs free energy revealed minimal structural changes and highlighted the stable conformational state of hIL1β upon Quercetin binding, suggesting a stabilizing effect of Quercetin. These observations suggest Quercetin’s potential in the development of new treatments for endodontic diseases, which may lead to improved clinical outcomes and reduced recurrence rates.