PDF(Pubmed)
Abstract：
In 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.
摘要：
在目前的研究中,我们利用分子建模和模拟方法来定义牛蛙菊粉的潜在分子靶标，包括炎症蛋白如iNOS,COX-2,TNF-α,IL-6和IL-1β。分子对接结果揭示了这些靶标的潜在相互作用和良好的结合亲和力；然而，IL-1β,COX-2和iNOS被鉴定为菊粉的最佳靶标。基于分子模拟的稳定性评估表明，菊粉可以主要靶向iNOS，也可能在DSS诱导的结肠炎期间补充靶向COX-2和IL-1β，以减少这些炎症机制的作用。此外，残余柔韧性，氢键,据报道，结构填料具有均匀的轨迹，在整个模拟过程中没有明显的扰动。使用主成分分析（PCA）对模拟轨迹内的蛋白质运动进行聚类。IL-1β-菊粉复合物，大约70%的总运动归因于前三个特征向量，而剩余的运动由剩余的特征向量贡献。相比之下,对于COX2-菊粉复合物，总运动的75%归因于特征向量。此外，在iNOS-菊粉复合物中，前三个特征向量占总运动的60％。此外，iNOS-菊粉复合物通过前三个特征向量对总运动贡献了60％。为了探索突变后热力学上有利的变化，进行了运动模式分析。自由能景观（FEL）结果表明，IL-1β-菊粉以最低的能量达到单一构象，而COX2-菊粉和iNOS-菊粉各表现出两种最低能量构象。IL-1β-菊粉和COX2-菊粉的总结合自由能为-27.76kcal/mol和-37.78kcal/mol，分别,而iNOS-菊粉在-45.89kcal/mol时表现出最佳的结合自由能结果。这表明iNOS比其他两种复合物具有更强的药理学潜力。因此，需要进一步的实验来使用菊粉靶向iNOS和减少DSS诱导的结肠炎和其他自身免疫性疾病。
