分子对接技术预测丹酚酸B对TGF-β/Smads信号通路的潜在作用靶点
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摘要
目的利用分子反向对接方法,探索丹酚酸B在TGF-β/Smads通路中的潜在作用靶点,为研究丹酚酸B干预上皮-间充质转化与纤维化机制提供参考依据。方法通过查阅文献寻找与TGF-β/Smads信号通路有关的药物靶点,构建TGF-β/Smads信号通路蛋白靶点结构数据集,通过分子对接软件AutoDockVina,对丹酚酸B和结构数据集中的蛋白分子进行反向分子模拟对接,根据丹酚酸B和各个靶点蛋白亲和力分数高低和对接构象相互作用的大小,筛选出潜在的靶点蛋白。结果根据AutoDockVina构象结合打分结果进行分析,分数最佳的是Snail(2y48)和Axin(2x39),均为-10.9分。Chimera构象检视显示Snail的结构优于Axin,从得分总体情况分析,Axin优于Snail。结论推测Snail、Axin可能为丹酚酸B潜在的药物作用靶点蛋白。
Objective To explore the potential drug target of salvianolic acid B in TGF-β/Smads signaling pathway by molecular reverse docking method,and provide references for study of salvianolic acid B on EMT and fibrosis. Methods The database of TGF-β/Smads pathway target protein structure was constructed by literature review. AutoDock Vina was used to perform the reversed molecular docking of salvianolic acid B and the protein molecules in structure database. The potential target proteins were screened out on the basis of the interaction between the affinity fraction of salvianolic acid B and the TGF-β/Smads pathway proteins. Results According to the combine scoring results of AutoDock Vina,the best targets were Snail(2 y48) and Axin(2 x39),-10.9 point. Chimera conformation revealed that the docking effect of Snail was better than Axin. However,overall scoring showed that Axin was better than Snail. Conclusion Snail and Axin are the potential drug targeting proteins of salvianolic acid B.
Objective To explore the potential drug target of salvianolic acid B in TGF-β/Smads signaling pathway by molecular reverse docking method,and provide references for study of salvianolic acid B on EMT and fibrosis. Methods The database of TGF-β/Smads pathway target protein structure was constructed by literature review. AutoDock Vina was used to perform the reversed molecular docking of salvianolic acid B and the protein molecules in structure database. The potential target proteins were screened out on the basis of the interaction between the affinity fraction of salvianolic acid B and the TGF-β/Smads pathway proteins. Results According to the combine scoring results of AutoDock Vina,the best targets were Snail(2 y48) and Axin(2 x39),-10.9 point. Chimera conformation revealed that the docking effect of Snail was better than Axin. However,overall scoring showed that Axin was better than Snail. Conclusion Snail and Axin are the potential drug targeting proteins of salvianolic acid B.
引文
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[11] DAVE N,GUAITA-ESTERUELAS S,GUTARRA S,et al. Functional cooperation between Snail1 and twist in the regu-lation of ZEB1 expression during epithelial to mesenchymal transition[J]. J Biol Chem,2011,286(14):12024-12032.
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[13] GUARINO M,TOSONI A,NEBULONI M. Direct contribution of epithelium to organ fibrosis:epithelial-mesenchymal transition[J]. Hum Pathol,2009,40(10):1365-1376.
[14] LUO Wen,LIN Shengcai. Axin:a master scaffold for multiple signaling pathways[J]. Neurosignals,2004,13(3):99-113.
[15] LIU Wei,RUI Hongliang,WANG Jifeng,et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia[J]. EMBO J,2006,25(8):1646-1658.
[16] GUO Xing,RAMIREZ A,WADDELL D S,et al. Axin and GSK3- control Smad3 protein stability and modulate TGF-β signaling[J]. Genes Dev,2008,22(1):106-120.
[17] FURUHASHI M,YAGI K,YAMAMOTO H,et al. Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway[J]. Mol Cell Biol,2001,21(15):5132-5141.
[2] YU Fujun,LU Zhongqiu,CHEN Bicheng,et al. Salvianolic acid B-induced microRNA-152 inhibits liver fibrosis by attenuating DNMT1-mediated Patched1 methylation[J]. J Cell Mol Med,2015,19(11):2617-2632.
[3] LIU Qingmei,CHU Haiyan,MA Yanyun,et al. Salvianolic Acid B attenuates experimental pulmonary fibrosis through inhibition of the TGF-β signaling pathway[J]. Sci Rep,2016,6:27610.
[4] 卢彬,王芳,蒋泓,等. 丹酚酸B对TGF-β1诱导大鼠黏连成纤维细胞增殖和细胞外基质合成的影响[J]. 中国新药杂志,2017,26(8):930-935.
[5] DERYNCK R,MUTHUSAMY B P,SAETEURN K Y. Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition[J]. Curr Opin Cell Biol,2014,31:56-66.
[6] DERYNCK R,ZHANG Y E. Smad-dependent and Smad- independent pathways in TGF-β family signalling[J]. Nature,2003,425(6958):577-584.
[7] AHMED S,NAWSHAD A. Complexity in Interpretation of embryonic epithelial-mesenchymal transition in response to transforming growth factor-β signaling[J]. Cells Tissues Organs,2007,185(1/3):131-145.
[8] TONG Zhuting,CAI Muyan,WANG Xiaoguang,et al. EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin[J]. Oncogene,2012,31(5):583-594.
[9]DONG Chenfang,WU Yadian,WANG Yifan,et al. Interaction with Suv39H1 is critical for Snail-mediated E-cadherin repression in breast cancer[J]. Oncogene,2013,32(11):1351-1362.
[10] PEINADO H,OLMEDA D,CANO A. Snail,Zeb and bHLH factors in tumour progression:an alliance against the epithelial phenotype[J] Nat Rev Cancer,2007,7(6):415-428.
[11] DAVE N,GUAITA-ESTERUELAS S,GUTARRA S,et al. Functional cooperation between Snail1 and twist in the regu-lation of ZEB1 expression during epithelial to mesenchymal transition[J]. J Biol Chem,2011,286(14):12024-12032.
[12] LAMOUILLE S,XU J,DERYNCK R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Bio,2014,15(3):178-196.
[13] GUARINO M,TOSONI A,NEBULONI M. Direct contribution of epithelium to organ fibrosis:epithelial-mesenchymal transition[J]. Hum Pathol,2009,40(10):1365-1376.
[14] LUO Wen,LIN Shengcai. Axin:a master scaffold for multiple signaling pathways[J]. Neurosignals,2004,13(3):99-113.
[15] LIU Wei,RUI Hongliang,WANG Jifeng,et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia[J]. EMBO J,2006,25(8):1646-1658.
[16] GUO Xing,RAMIREZ A,WADDELL D S,et al. Axin and GSK3- control Smad3 protein stability and modulate TGF-β signaling[J]. Genes Dev,2008,22(1):106-120.
[17] FURUHASHI M,YAGI K,YAMAMOTO H,et al. Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway[J]. Mol Cell Biol,2001,21(15):5132-5141.