基于反向对接法的大黄酸抗炎作用的分子机制研究

Study on anti-inflammatory mechanism of rhein based on reverse docking method

目的:利用反向对接技术以大黄酸为研究对象筛选出大黄酸的炎症靶标蛋白。方法:获取Toll样受体/核因子(4TLR4/NF-κB)、p38促分裂原活化蛋白激酶(P38mitogen-activated protein kinases,P38 MAKP)和Janus激酶-信号转导转录激活因子(Janus kinase 2/signal transducer and activator of transcription 3,JAK2/STAT3)3条炎症通路上的30个蛋白的晶体学结构以及大黄酸的化学结构;利用AutoDockTools对所有晶体学结构进行标准化处理;通过AutoGrid对靶标蛋白的活性位点进行计算;利用AutoDock对大黄酸进行反向对接模拟实验;对得到的对接结果进行筛选,根据对接自由能的高低,筛选出亲和力高的靶蛋白;对筛选得到的靶蛋白进行作用力分析并作图。结果:反向筛选得到3个与大黄酸具有高亲和性的靶蛋白,分别为P38、PI3Kγ、JAK2。结论:大黄酸是通过抑制P38、PI3Kγ、JAK2靶蛋白,进而阻碍炎症信号传递,影响下游蛋白的表达,发挥抗炎作用。

Objective：To investigate the mechanism of anti-inflammation of rhein through the approach of reverse docking,which was utilized to dock rhein with proteins in the signal pathways of NF-κB、P38and JAK2/STAT3.Methods：Thirty proteins of NF-κB、P38and JAK2/STAT3 pathway were obtained from PDB website,the structure of rhein was obtained from PubChem website.All the proteins were processed with standardization disposal of AutoDockTools.Then AutoGrid was utilized to calculate the grids of active sites.The docking result has been ranked according to docking energy,for the purpose of selecting out the proteins with high affinity for rhein.Results：Three target proteins including P38,PI3Kγand JAK2 were found to interact with rhein with high affinity.Conclusion：Anti-inflammation of rhein relates to its function of competitive inhibition for the 3target proteins,and the behavior of rhein results in the obstruction to signal pathways.Finally the purpose of treatment for inflammation has been achieved by this method.