Predicting potential antitumor targets of Aconitum alkaloids by molecular docking and protein-ligand interaction fingerprint
Predicting potential antitumor targets of Aconitum alkaloids by molecular docking and protein-ligand interaction fingerprint
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通过分子对接和蛋白质-配体相互作用指纹预测乌头生物碱的潜在抗肿瘤靶点
DOI：
10.1007/s00044-016-1553-7
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发表时间：
2016-06-01
影响因子：
2.6
通讯作者：
Meng, Fan-hao
中科院分区：
文献类型：
--
作者：
Liang, Jing-wei;Zhang, Ting-jian;Meng, Fan-hao
乌头、川乌、乌头等毛花科植物中均含有乌头类化合物，既是有效成分，又是有毒成分。为了寻找乌头生物碱潜在的抗肿瘤靶点，本研究从蛋白质数据库(http://www.rcsb.org)，)中选择了20个不同类型的抗肿瘤靶蛋白，利用Sybyl-X1.1和分子操作环境(MOE)2008中的分子对接模块，通过分子对接方法筛选排名靠前的蛋白质，并用分子操作环境中的蛋白质-配体相互作用指纹图谱对筛选结果进行了验证。新乌头碱与热休克蛋白90(HSP90)对接后呈C型构象，与格尔达霉素的ANSA环相似。PLIF结果表明，它们具有许多与HSP90相互作用的共同氨基酸残基；同样，云乌头碱与聚腺苷二磷酸核糖聚合酶-1(PARP-1)的抑制物具有相似的构象。
Aconitine compounds are found in Aconitum Ouwu head, Chuan Wu, Aconitum, and other Ranunculaceae aconitum plants, which are not only active ingredient but also toxic component. In present study, 20 antitumor target proteins of different types were selected from Protein Data Bank (http://www.rcsb.org), for the purpose of finding potential antitumor targets of aconitum alkaloids, top ranked proteins were screened by molecular docking method, using the docking module in Sybyl-X 1.1 and Molecular Operating Environment (MOE) 2008, and screening result was verified by protein-ligand interaction fingerprint (PLIF) in MOE. Mesaconitine showed a C-shaped conformation when docking into heat-shock protein 90 (HSP90), which was similar with ANSA ring of geldanamycin. And the PLIF indicated that they shared many common amino acid residues interacted with HSP90; equally, Yunaconitine was found having similar conformation with the inhibitor of poly ADP-ribose polymerase-1 (PARP-1).