基于分子对接技术、分子动力学模拟中药复方益糖康防治糖尿病肾病作用机制研究

Mechanism Research of Chinese Medicine Compound Yitangkang(益糖康)Improving Diabetic Nephropathy Based on Bioinformatics Analysis,Molecular Docking and Molecular Dynamics Technology

目的通过生信分析、分子对接及分子动力学技术探讨中药复方益糖康(YTK)防治糖尿病肾病的作用机制。方法通过网站、数据库及文献检索获取YTK的有效成分及糖尿病肾病疾病靶点,经筛选后进行生信分析。结合生信分析结果及CTD数据库选择5个重要蛋白受体,分别与YTK符合筛选标准的有效成分通过Auto Dock Vina软件进行分子对接,将分子对接结果中结合能较强且具有继续研究意义的构象应用分子动力学技术进行进一步分析。结果槲皮素、黄芩素、山柰酚、丹参酮II等22个化合物可能是YTK防治糖尿病肾病的重要活性成分,涉及氧化应激反应、调节活性氧代谢、炎症反应等多个生物过程及AGE-RAGE、TNF、PI3K-Akt、VEGF、p53、mTOR等多个信号通路;重要蛋白受体为PTGS1、PTGS2、NCOA2、HSP90AA1、RXRA,研究上述重要蛋白受体对精准阐释糖尿病肾病的发病与防治有重要的意义。YTK筛选的活性成分与受体结合能平均值为-8.16 kcaL·moL^(-1),超过96.36%的结合能低于-5.6 kcaL·moL^(-1),证实了其防治DN效果良好。baicalein-HSP90AA1、quercetin-PTGS2作为有继续研究意义的构象进一步进行分子动力学模拟,结果均可以稳定地结合,为范德华势能和静电作用、氢键作用共同作用的结果。结论研究揭示了YTK防治糖尿病肾病的潜在分子机制,为后续研究提供理论依据及参考。

Objective Based on bio-analysis,molecular docking and molecular dynamics techniques to explore the mechanism of the active ingredients in the Chinese medicine compound Yitangkang(益糖康,YTK)in preventing and treating diabetic nephropathy(DN).Methods The effective components of YTK and the target of diabetic nephropathy were obtained through website,database and literature search,and after screening,the unique database of Shanghai Baipu Biotechnology Co.,Ltd.was used for biometric analysis.Based on the results of biosynthesis analysis and CTD database,five important protein receptors were selected,and the active ingredients that meet the screening criteria of YTK were molecularly docked through Auto Dock Vina software,and the molecular docking results had a strong binding energy and a conformation that was meaningful for further research.Using molecular dynamics technology for further analysis.Results Quercetin,baicalein,kaempferol,tanshinone II and other 22 compounds may be important active components of YTK in the prevention and treatment of diabetic nephropathy,involving oxidative stress response,regulation of reactive oxygen metabolism,inflammation and other biological processes and AGE-RAGE,TNF,PI3 K-Akt,VEGF,p53,mTOR and many other signaling pathways;important protein receptors are PTGS1,PTGS2,NCOA2,HSP90 AA1,RXRA.The study of the above-mentioned important protein receptors was important to accurately explain the incidence and prevention of diabetic nephropathy meaning.The average binding energy of active ingredients and receptors screened by YTK was-8.16 kcal·mol^(-1),and the binding energy of more than 96.36%was lower than-5.6 kcal·mol^(-1),confirming its good effect in preventing DN.Baicalein-HSP90 AA1 and quercetinPTGS2 were further molecular dynamics simulations as meaningful conformations for further research,and the results could be combined stably,which was the result of the combined effect of van der Waals force,electrostatic interaction,and hydrogen bond interaction.Conclusion This study reveals the potential molecular mechanism of the Chinese medicine Yitangkang in preventing and treating diabetic nephropathy,and provides theoretical basis and reference for follow-up research.