基于分子对接技术的常用降糖中药有效成分虚拟筛选

Virtual Screening for Effective Components in Commonly Used Anti-diabetic Traditional Chinese Medicines Based on Molecular Docking Technology

目的:运用分子对接技术分析常用降糖中药效应物质基础及其作用机制,为降糖中药现代研究提供理论依据。方法:基于文献搜集降糖中药化学成分并构建其结构数据库,以二肽基肽酶-Ⅳ等7个糖尿病治疗靶标为分子对接的研究对象,通过Sybyl软件的Surflex-Dock分子对接模块进行虚拟筛选,以打分函数Total-Score为标准评价中药成分与靶标间相互作用,以Total-Score等于7为阈值,筛选出与各靶标结合较好的化学成分,并与已上市降糖西药进行类药性比较。结果:与二肽基肽酶-Ⅳ,糖原合酶激酶-3,过氧化酶增殖因子活化受体γ,α-葡萄糖苷酶,葡萄糖激酶,钠-葡萄糖共转运蛋白2和血管紧张素转化酶能较好结合的化学成分分别有52,28,32,150,47,41,33个。通过虚拟筛选得到的这些小分子化合物与已上市降糖西药具有相似的类药性性质。结论:分子对接技术在一定程度上解释了降糖中药的效应物质基础与作用机制,为降糖中药现代研究提供了线索。

Objective： To analyze pharmacodynamic material basis and mechanism for commonly used anti-diabetic traditional Chinese medicine by molecular docking technology,in order to provide a theoretical basis for modern studies on anti-diabetic traditional Chinese medicines. Method： Chemical components of anti-diabetic traditional Chinese medicines were collected based on literatures to establish the structure database. With seven diabetes therapeutic targets such as dipeptidyl peptidase-IV as the study objects,virtual screening was conducted by the Surflex-Dock module of Sybyl software. With scoring function Total-Score as the standard, interactions between components of traditional Chinese medicine and targets were evaluated. With the Total-Score value at 7,molecules with high score were screened out to further compared with anti-diabetic western medicines in the market in terms of the drug-likeness. Result： There were 52,28,32,150,47,41 and 33 chemical components well combined with dipeptidyl peptidase-IV, glycogen synthase kinase-3, peroxisome proliferator-activated receptor gamma,alpha-glucosidaseare,glucokinase,sodium glucose cotransporter 2 and angiotensin converting enzyme.These small molecule compounds obtained by virtual screening were similar to the western medicine in the market in terms of the drug-likeness. Conclusion： Molecular docking technology can explain pharmacodynamic material basis and mechanism of anti-diabetic traditional Chinese medicines to some extent and provide clues for modern studies on anti-diabetic traditional Chinese medicines.