基于分子对接的鸡血藤抗血栓活性成分的筛选研究

Study on Screening of Antithrombotic Active Components of Spatholobi Caulis Based on Molecular Docking Technology

关键词:  鸡血藤  抗血栓活性  分子对接  虚拟筛选

Key words:  Spatholobi Caulis  antithrombotic  molecular docking  virtual screening

摘要:

目的 采用分子对接技术筛选鸡血藤中抗血栓形成的活性成分。方法 检索TCMSP得到鸡血藤所有化学成分，结合口服生物利用度（oral bioavailability，OB）≥ 30%以及类药性（drug likeness，DL）≥ 0.18，筛选出活性化合物，利用PharmMapper初步预测鸡血藤的活性成分的对应靶点，选择与抗血栓形成相关的靶点，以Drug Bank中对血栓形成有抑制作用并已上市或者正在进行临床试验的小分子药物为阳性对照，再以AutoDock Vina进行分子对接。结果 共筛选出鸡血藤活性化合物23个，抗血栓相关靶点4个，以低于活性化合物最低结合能平均值的化合物为最终阳性结果，对比分析原配体、阳性对照和鸡血藤活性化合物作用于各靶点的主要活性位点，阐明鸡血藤抗血栓的机制可能与其抑制内外凝血途径有关。结论 分子对接技术不仅为鸡血藤活血作用的机制研究提供了参考，也为进一步开发安全有效的抗血栓类单体提供了研究方向。

Abstract:

OBJECTIVE To screen the antithrombotic active components of Spatholobi Caulis by molecular docking technology. METHODS Compounds of Spatholobi Caulis were collected by searching TCMSP. Compounds with oral bioavailability(OB) ≥ 30% and drug likeness(DL) ≥ 0.18 were considered to be the active components in Spatholobi Caulis. These active components were uploaded to PharmMapper to predict the corresponding targets, and the targets related to antithrombotic were selected. In addition, the small-molecules drugs which had antithrombotic effect that had been listed or undergoing clinical trials from Drug Bank database were set as positive references. AutoDock Vina was applied to perform molecular docking. RESULTS Twenty-three compounds of Spatholobi Caulis and 4 potential targets which showed close correlation with antithrombotic were obtained. The compound with a binding energy below the average energy was selected as the final positive result. The antithrombotic effects of Spatholobi Caulis were finally explained by compared the main active sites of the test compounds with original ligands and references, which were related to the inhibition of intrinsic and extrinsic coagulation pathways. CONCLUSION Molecular docking not only provides a certain reference to explore the mechanisms of Spatholobi Caulis in invigorating the circulation of blood, but also provides research direction for the development of safe and effective antithrombotic drugs in the future.