网络药理学与分子对接技术指导下土大黄苷对慢性粒细胞白血病作用机制研究

Interaction between traditional Chinese medicine rhaponticin and genes associated with chronic myelocytic leukemia and its mechanism based on molecular docking technology and network pharmacology

目的近年来,蛋白质相互作用网络及分子对接技术成为中药现代化研究领域十分活跃的一部分,逐渐成为链接中药应用与现代化的重要纽带。本研究基于分子对接技术与网络药理学分析,探讨中药大黄活性成分土大黄苷与慢性粒细胞白血病(chronic myelocytic leukemia,CML)相关基因之间的相互作用,寻求土大黄苷作用与CML的可能机制。方法前期研究中构建了CML蛋白质相互作用网络,并筛选了CML关键靶点蛋白,作为本研究的受体;通过软件Chemoffice 8.0构建土大黄苷的分子结构,导入SYBYL软件中,进行一系列数据处理,作为本研究的配体。利用SYBYL 8.1软件的Surflex-Dock模块进行分子对接,用配体-受体亲和力的一致性评分函数进行打分,并对氢键及其结合部位进行观察、分析。进一步对分子对接结果进行文献验证。结果得到土大黄苷与CML19个相关基因之间的分子对接评分及氢键数,其中与JUN(2G01)受体对接得分及氢键数是最高的,说明土大黄苷与JUN(2G01)结合最好,可以推断JUN(2G01)是土大黄苷优先选择的作用受体。其次,得分较高的还有SRC(SRC)、JAK2(5AEP)、MAPK14(2YIX)、FRAP1(3OAW)、MAPK8(3PZE)和PARP1(1U5Y)等。结论大黄活性成分土大黄苷对CML的作用机制是多靶点、多途径相互作用的,其作用受体可能与JUN、SRC、JAK2、MAPK14、FRAP1、MAPK8和PARP1等基因相关。

OBJECTIVE In recent years,protein-protein interaction networks and molecular docking technology become a very active research areas for traditional Chinese medicine（TCM）modernization and gradually become the important link between the application and modernization of Chinese medicine.This paper is based on the analyses of molecular docking technology and network pharmacology,studying the interaction between TCM rhaponticin and genes associated with chronic myelocytic leukemia（CML）and analyzing the mechanism of rhaponticin in treating chronic myelocytic leukemia.METHODS In prior research,we built the CML protein interaction networks and screened the CML key protein targets as the receptor of this study.We used the Chemoffice 8.0to build the molecular structure of the rhaponticin which was imported in the SYBYL software.After a series of data processing,it became the ligand of this study.We used Surflex-Dock Surflex of the SYBYL 8.1software to do molecular docking,using the consistency of the ligand and receptor affinity to score,then observing and analyzing the hydrogen bonding and combining sites in order to finally verify the molecular docking results.RESULTS We got results of molecular docking score and hydrogen bond between rhaponticin and 19 genes.We could see that rhaponticin and JUN（2G01）had the highest docking score which demonstrated the two combined the best.From the results,we could infer that JUN（2G01）was the preference receptor for rhaponticin and SRC（SRC）,JAK2（5AEP）,MAPK14（2YIX）,FRAP1（3OAW）,MAPK8（3PZE）,PARP1（1U5Y）had high scores.CONCLUSION nunction of rhaponticin involves multiple targets and multiple ways and the receptor may be related to JUN,SRC,JAK2,MAPK14,FRAP1,MAPK8 and PARP1.