摘要
目的:运用虚拟筛选技术从传统中药数据库(traditional Chinese medicine database platform,TCMSP)中寻找HIV-1整合酶的中药小分子抑制剂。方法:以整合酶与细胞因子LEDGF/P75相互作用位点为靶点,运用分子对接技术进行首轮筛选,然后运用ADME/T预测进行第二轮筛选,最后基于靶点与药物相互作用位点进行第三轮筛选。结果:以原配体(4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy)-methyl]-benzoic acid,D77)为阳性对照,筛选出2个类药性良好的天然小分子化合物,二者与HIV-1整合酶亲和力及相互作用基团均优于D77(新型的HIV-1整合酶抑制剂),并且确定了它们的中草药来源。结论:成功建立一整套高通量虚拟筛选HIV-1整合酶抑制剂的策略,该研究结果可促进从传统中药库中提取、设计以及实验合成新的抗艾滋病药物。
Objective： To search small molecule inhibitors for HIV-1 intergrase from traditional Chinese medicine database platform（ TCMSP） by using the virtual screening technology. Method： The interacting site between HIV-1 intergrase andcytokine LEDGF / P75 were taken as target. The molecular docking technology was used for the first round of screening,then the ADME / T prediction was adopted for the second round of screening,and finally the target point andthe interacting site were based for the third round of screening. Result： The free binding energy of original ligand（ 4-[（ 5-bromo-4-{ [2, 4-dioxo-3-（ 2-oxo-2-phenylethyl）-1, 3-thiazolidin-5-ylidene]methyl}-2-ethoxyphenoxy）-methyl]-benzoic acid,D77） was be used as positive control to screen out two natural micro-molecule compounds with good drug likeness. Thenatural micro-molecule compounds, HIV-1intergraseandinteractive perssad showed a superioraffinity to D77（ a new-typeintergrase inhibitor）. Their sources of traditional Chinese medicine were determined. Conclusion： This study successfully established a high-throughput virtual screening strategy for HIV-1 intergrase inhibitors,and provides an important reference and theoretical basis for the extraction of anti-AIDS compounds from Chinese herbal medicine and the design of anti-AIDS drugs.
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2016年第19期159-164,共6页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81473782)
国家级大学生创新创业训练计划项目(201510716494)
