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目的:运用计算机虚拟筛选技术从传统中药数据库(TCMSP)中快速搜索HIV-1蛋白酶(Protease,PR)的中药小分子抑制剂。方法:采用Scripps研究所的Auto Dock Vina软件,对蛋白质晶体结构数据库PDB中PR与小分子抑制剂沙奎那韦(Saquinavir)形成的复合物(PDB代码:1HXB)三维结构活性部位进行分析,基于传统中药配体库进行分子对接初次筛选。综合运用传统中药系统药理学数据库及分析平台TCMSP及Accelrys公司开发的Discovery Studio 2.5分子模拟软件包内TOPKAT模块计算药代动力学参数和毒性预测对分子对接结果进行2次筛选。结果:以原配体(沙奎那韦)为阳性对照,筛选出传统中药库TCMSP中2个类药性良好的化学成分与PR亲和力高于上市的抗艾滋病药物沙奎那韦的天然小分子化合物,并且确定了它们的中草药来源。结论: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 rapidly search traditional Chinese medicine small molecule inhibitor of HIV-1 protease (Protease, PR) from traditional Chinese medicine database (TCMSP) by using computer virtual screening technology. Methods: Based on Auto Dock Vina software of Scripps Institute, the three-dimensional structural active sites of the complex formed by PR with small molecule inhibitor Saquinavir in PDB of PDB were analyzed. Traditional Chinese medicine ligand library for molecular docking of the initial screening. The molecular docking results were screened twice using the traditional Chinese medicine system pharmacology database and analysis platform TCMSP and the TOPKAT module of Discovery Studio 2.5 molecular simulation software package developed by Accelrys to calculate the pharmacokinetic parameters and toxicity prediction. RESULTS: The original ligand (saquinavir) was used as positive control to screen out two traditional Chinese medicinal herb TCMSPs with good chemical constituents and natural small molecule compounds with PR affinity higher than the listed anti-AIDS drug saquinavir , And identified their source of Chinese herbal medicine. Conclusion: The results of this study can facilitate the extraction, design and experimental synthesis of new anti-AIDS drugs from traditional Chinese medicine repositories.