目的 应用虚拟筛选方法预测雷公藤内酯醇作用靶标， 以期阐明雷公藤治疗银屑病机制。方法 根据银屑病的病理学特征，从PDTD(Potential Drug Target Database)数据库中筛选到的一批与雷公藤内酯醇可能发生相互作用的蛋白质中，选取视黄酸结合蛋白2、Caspase-1、蛋白S100-A9、视黄酸受体-alpha、视黄酸受体-beta、视黄酸受体-gamma、VEGFR以及血管生成素-1受体等8种可能与银屑病治疗相关的蛋白质靶标，利用Autodock 4.2分子对接软件，对雷公藤内酯醇与上述蛋白质靶标进行了逐一的精细对接和分析。 结果 通过比较其结合自由能、预测其抑制常数，并分析雷公藤内酯醇与蛋白质靶标的相互作用，发现雷公藤内酯醇与视黄酸结合类蛋白的相互作用最为强烈。结论 雷公藤内酯醇治疗银屑病的药理学机制可能与视黄酸相关信号通路有关，我们的研究为进一步的药理学机制研究奠定了基础.
Abstract
To explore the mechanism of Chinese herb Tripterygium wilfordii Hook f. in treatment with psoriasis,the virtual screening method was used to predict the potential protein targets of triptolide, one of the main effective compounds in Tripterygium. METHODS According to the pathological features of psoriasis,eight proteins were selected, including retinoic acid binding protein 2, caspase-1, protein S100-A9, retinoic acid receptor-α, β and γ, VEGFR, and angiopoietin-1 receptor, from the protein pool we got by screening potential drug target database with molecular docking method. A software AUTODOCK 4.2 was used to find the potential protein targets of triptolide by careful matching and analysis of interaction between triptolide and each of these eight proteins one by one. RESULTS The docking results, combined with the comparation of their binding energy and inhibition constants, showed that the interactions between triptolide and those retinoic acid binding proteins are most strong. CONCLUSION The pharmaceutical mechanism of triptolide in treatment of psoriasis may be related with retinoic acid related signaling pathway. Our study may provide some valuable clues in the study of pharmaceutical mechanism of triptolide.
关键词
银屑病 /
雷公藤内酯醇 /
蛋白质靶标 /
计算机模拟筛选
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Key words
psoriasis /
triptolide /
protein target /
computer screening
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中图分类号：
Q51
O629
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参考文献
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脚注
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基金
国家自然科学基金资助项目(81072712)；国家基础科学人才培养基金项目(J1103512、J1210026)；江苏省自然科学基金(BK2011573)
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