摘要
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 report the preliminary result of virtual screening small molecule inhibitors of tumor necrosis factor-α（TNF-α） based on the traditional Chinese medicine database.Method： Based on the optimized complex structure of TNF-α bound with specific inhibitor（compound 307,PDB code 2AZ5）,computer-aided structure-based virtual screening against Chinese Natural Product Database（CNPD） was conducted to determine the occurrence of herb-based TNF-α inhibitors in the software package Discovery Studio（2.5） of Accerlrys company.The virtual screening results were further filtered by predictive ADME simulation and predictive toxic simulation.Result： According to the dockscore of original inhibitor（compound 307） and the receptor as threshold value,12 drug-like molecules were predicted to have good interactions with TNF-α.Conclusion： It is expected that the TNF-α small molecule inhibitors identified at present study could be helpful for development of new drug to treat rheumatoid arthritis and inflammatory bowel disease.
出处
《中国实验方剂学杂志》
CAS
北大核心
2010年第13期199-202,共4页
Chinese Journal of Experimental Traditional Medical Formulae
基金
广东省自然科学基金课题(9151063201000050)
广东省中医药局建设中医药强省科研课题(2008334)
关键词
计算机虚拟筛选
中药
肿瘤坏死因子-Α
virtual screening； traditional Chinese medicine； tumor necrosis factor-α
