基于计算机辅助药物设计研究白术挥发油的主要成分作用靶点及药效预测  

Study on the Main Components of Atractylodes Macrocephala Volatile Oil Target and Pharmacodynamic Prediction based on Computer Aided Drug Design

作　　者：于启蒙 张新超 孟慧琴 张霖 朱德志 章伟 王爱东[1] Yu Qi-meng;Zhang Xin-chao;Meng Hui-qin;Zhang Lin;Zhu De-zhi;Zhang Wei;Wang Ai-dong

机构地区：[1]黄山学院,黄山2544041

出　　处：《化工设计通讯》2020年第10期152-154,198,共4页Chemical Engineering Design Communications

基　　金：全国大学生创新创业训练计划项目资助项目(201810375043);黄山地道中药祁术主要成分作用靶点及作用机理(201810375113)。

摘　　要：[目的]基于计算机辅助药物设计(CADD)研究白术挥发油中的白术内酯Ⅰ、白术内酯Ⅱ、白术内酯Ⅲ、苍术酮、β-榄香烯、香橙烯和异香橙烯分子潜在作用靶点,并预测这7个分子的药效。[方法]查阅文献建立含有上述7个配体分子结构的分子库,使用Discovery Studio 2016(DS)软件对分子库的分子结构进行优化,运用DS中的反向找靶(Target Fishing)功能模块对含有超过117000个药效团模型的PharmaDB药效团数据库搜索;根据反向找靶的运行结果,筛选出配体与药效团的契合值(Fit value)≥0.9且对应打分最高的靶点蛋白。从PDB数据库下载靶点蛋白,运用DS中的分子对接(Molecular Docking)技术查看筛选出的配体分子与对应靶点蛋白的非键相互作用情况。[结果]反向找靶结果中筛选出6个靶点蛋白分别为酪蛋白激酶2、MDMX蛋白、维生素D3羟化酶、细胞周期蛋白A和细胞周期蛋白依赖性蛋白激酶2的复合物、CDC样激酶3和酪蛋白激酶2α亚基。根据分子对接的结果并结合生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库预测,白术挥发油的主要成分具有潜在的抗肿瘤、免疫调节和抗炎的药效作用。[Objective]Based on computer aided drug design(CADD),the potential targets of atractylolideⅠ,atractylolideⅡ,atractyloneⅢ,atractylone,β-elemene,limonene and isocaryotene in Atractylodes macrocephala volatile oil were studied,and the pharmacodynamics of these seven molecules were predicted.[Methods]literature review was conducted to establish a molecular library containing the seven ligands mentioned above.The discovery studio 2016(DS)software was used to optimize the molecular structure of the library,and the reverse target in DS was used The functional module searches pharmadb pharmacophore database containing more than 117000 pharmacophore models;according to the operation results of reverse target searching,the target protein with the matching value of ligand and pharmacophore≥0.9 and corresponding to the highest score was selected.The target proteins were downloaded from PDB database,and the non bond interactions between the selected ligands and the corresponding target proteins were checked by molecular docking technology in DS.[results]six target proteins were screened from the reverse targeting results,which were casein kinase 2,mdmx protein,vitamin D3 hydroxylase,cyclin A and cyclin dependent protein kinase 2 complex,CDC like kinase 3 and casein kinase 2 subunit NCBI database predicted that the main components of Rhizoma Atractylodis Macrocephalae had potential antitumor,immunomodulatory and anti-inflammatory effects.

关 键 词：白术 反向找靶 分子对接 药效预测 计算机辅助药物设计 

分 类 号：R285[医药卫生—中药学] R914.2[医药卫生—中医学]