Molecular modeling and simulation approaches to characterize potential molecular targets for burdock inulin to instigate protection against autoimmune diseases

Abstract

AbstractIn the current study, we utilized molecular modeling and simulation approaches to define putative potential molecular targets for Burdock Inulin, including inflammatory proteins such as iNOS, COX-2, TNF-alpha, IL-6, and IL-1β. Molecular docking results revealed potential interactions and good binding affinity for these targets; however, IL-1β, COX-2, and iNOS were identified as the best targets for Inulin. Molecular simulation-based stability assessment demonstrated that inulin could primarily target iNOS and may also supplementarily target COX-2 and IL-1β during DSS-induced colitis to reduce the role of these inflammatory mechanisms. Furthermore, residual flexibility, hydrogen bonding, and structural packing were reported with uniform trajectories, showing no significant perturbation throughout the simulation. The protein motions within the simulation trajectories were clustered using principal component analysis (PCA). The IL-1β–Inulin complex, approximately 70% of the total motion was attributed to the first three eigenvectors, while the remaining motion was contributed by the remaining eigenvectors. In contrast, for the COX2–Inulin complex, 75% of the total motion was attributed to the eigenvectors. Furthermore, in the iNOS–Inulin complex, the first three eigenvectors contributed to 60% of the total motion. Furthermore, the iNOS–Inulin complex contributed 60% to the total motion through the first three eigenvectors. To explore thermodynamically favorable changes upon mutation, motion mode analysis was carried out. The Free Energy Landscape (FEL) results demonstrated that the IL-1β–Inulin achieved a single conformation with the lowest energy, while COX2–Inulin and iNOS–Inulin exhibited two lowest-energy conformations each. IL-1β–Inulin and COX2–Inulin displayed total binding free energies of − 27.76 kcal/mol and − 37.78 kcal/mol, respectively, while iNOS–Inulin demonstrated the best binding free energy results at − 45.89 kcal/mol. This indicates a stronger pharmacological potential of iNOS than the other two complexes. Thus, further experiments are needed to use inulin to target iNOS and reduce DSS-induced colitis and other autoimmune diseases.