传统中药数据库中HIV-1蛋白酶抑制剂计算机虚拟筛选  

Computer Virtual Screening HIV-1 Protease Inhibitors Based on Traditional Chinese Medicine Database

作　　者：史海龙[1] 赵云飞[1] 陈哲[1] 

机构地区：[1]陕西中医药大学,陕西咸阳712046

出　　处：《辽宁中医药大学学报》2016年第10期73-78,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家级大学生创新创业训练计划项目(201410716001)

摘　　要：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：Using the technology of computer virtual screening from traditional Chinese medicine database platform（TCMSP）fast search small molecule inhibitors for HIV-1 protease（PR）. Methods：Based on the optimized complex structure of PR bound with specific inhibitor（saquinavir,PDB code 1HXB）,computer-aided structure-based virtual screening against TCMSP was conducted to determine the occurrence of herb-based PR inbitors in the software package Auto Dock Vina of the scripps institution. The virtual screening results were further filtered by predictive ADME simulation using TCMSP and simultaneously filtered by predictive toxic simulation using TOPKAT module from Discovery Studio 2.5 software package. Results：The free binding energy of original ligand（saquinavir）can be used as positive control,then not only obtained two compounds having a higher binding affinity than saquinavir,but also they have good drug-likeness. Their sources of traditonal Chinese medicine has been determined. Conclusion：This study provides an important reference and a theoretical basis for the extraction of antiviral compounds from Chinese herbal medicine and the design of anti- AIDS drugs.

关 键 词：HIV-1蛋白酶抑制剂 虚拟筛选 传统中药 

分 类 号：R512.91[医药卫生—内科学]