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目的:运用计算机虚拟筛选技术快速搜索肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的中药小分子抑制剂。方法:采用Accelrys公司Discovery Studio分子模拟软件包(版本2.5),对蛋白质晶体结构数据库PDB中TNF-α与小分子抑制剂(化合物307)形成的复合物(PDB代码:2AZ5)三维结构活性部位进行分析,通过ligandfit模块进行分子对接。运用药代动力学参数预测和毒性预测等模块对分子对接结果进行2次筛选。结果:以原配体(化合物307)的Dockscore值为阈值,筛选出中国天然产物数据库中12个类药性良好的化学成分与TNF-α存在较强的相互作用。结论:该研究结果可促进治疗类风湿性关节炎、炎性肠病等病的新型药物研制。
OBJECTIVE: To rapidly search small molecule inhibitors of tumor necrosis factor-α (TNF-α) by computer virtual screening. METHODS: Three-dimensional structural active sites of the complex formed by TNF-α and small molecule inhibitor (compound 307) (PDB code: 2AZ5) in PDB of protein crystal structure database were obtained by using Accelrys Discovery Studio molecular simulation software package (version 2.5) Analysis, molecular docking via ligandfit module. The molecular docking results were screened twice using pharmacokinetic parameters prediction and toxicity prediction. Results: Dockscore value of the original ligand (compound 307) was used as the threshold value to screen out the strong interaction between chemical composition of 12 Chinese medicines and TNF-α in Chinese natural product database. Conclusion: The results of this study can promote the development of new drugs for the treatment of rheumatoid arthritis and inflammatory bowel disease.