应用计算机模拟技术比较川芎与当归的分子特征

Comparison of ligusticum chuanxiong and angelica sinensis in molecular characteristics by using computer simulation technology

目的:比较川芎和当归的分子特征。方法:通过检索北京大学天然产物库,检索出川芎中的化合物89个、当归中的化合物90个,在Discovery studio模拟平台上建立川芎和当归化合物分子数据集,依托定量构效关系平台,分析2种中药中化合物分子数据集的化学空间特征。通过检索TTD数据库和相关文献,确定白细胞介素(interleukin,IL)1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)为川芎和当归治疗骨关节炎(osteoarthritis,OA)疼痛的作用靶点,从RCSB蛋白数据库下载其蛋白质-配体复合物结构,在Discovery studio模拟平台上建立其蛋白分子数据集。利用分子对接和生物网络技术,分别构建川芎和当归化合物-OA疼痛靶点作用网络,并比较其特征。结果:川芎和当归化合物分子数据集既具有相同或相近的化学空间,又具有不同的化学空间。川芎和当归化合物分子数据集化学空间中的分子量、氢键受体数目比较,组间差异均有统计学意义(t=2.549,P=0.012;χ~2=29.825,P=0.002);二者的脂水分配系数、氢键给体数目比较,组间差异均无统计学意义(t=1.583,P=0.115;χ~2=4.658,P=0.793)。川芎和当归化合物-OA疼痛靶点作用网络显示川芎和当归中的活性成分数目分别为26个和15个,且主要活性成分均为苯酞类化合物。2种中药的化合物-OA疼痛靶点作用网络的度、路中心、最近距离中心、拓扑系数比较,组间差异均无统计学意义(χ~2=6.422,P=0.491;t=-0.446,P=0.658;t=-1.908,P=0.063;t=-1.205,P=0.234);2种中药的化合物-OA疼痛靶点作用网络的平均最短路径长度比较,差异有统计学意义(t=2.032,P=0.048)。结论:川芎和当归中所含化合物在化学空间及作用网络特征方面存在一定程度的相似性,但在治疗OA疼痛方面,川芎比当归拥有更多的活性成分,二者配伍后具有更多样的理化性质,且存在潜在的协同作用。

Objective：To compare the molecular characteristics of ligusticum chuanxiong with those of angelica sinensis. Methods： Eighty - nine and ninety chemical compounds were searched out from ligusticum chuanxiong and angelica sinensis respectively by searching Peking University Natural Product Library to build ligustieum chuanxiong and angelica sinensis chemical compound molecular datasets on the Discovery studio simulation platform, and the chemical spatial characteristics of chemical compound molecular datasets of the two Chi- nese drugs were analyzed relying on the quantitative structure - activity relationship platform. Interleukin（IL） 1 ,IL - 6 and tumor necrosis factor -ct（ TNF -or）were identified as the targets of ligusticum chuanxiong and angelica sinensis for treatment of OA pain through retrieving TI＇D database and related literatures, and their protein - ligand compound structures were downloaded from RCSB protein database and the molecular datasets of protein were built on the Discovery studio simulation platform. The network of interaction between chemical compounds of ligusticum chuanxiong and targets of OA pain and between chemical compounds of angelica sinensis and targets of OA pain were built re- spectively by using molecular docking and bio - network technology, and their characteristics were compared with each other. Results ： The chemical compound molecular dataset of ligusticum chuanxiong was the same as or similar to that of angelica sinensis in chemical space, while they had other different chemical space. There was statistical difference in the molecular weight and number of hydrogen - bond accep- tot between chemical space of chemical compound molecular dataset of ligusticum chuanxiong and that of angelica sinensis（ t = 2. 549 ,P =0. 012 ;X2 = 29. 825 ,P = 0.002）, and there was no statistical difference in lipid - water partition coefficients and the number of hydrogen - bond donor between them（ t = 1. 583 ,P = 0. 115 ;X2 = 4. 658 ,P = 0. 793 ）. The network of interaction between chemical compounds of ligustic- um chuanxiong and targets of OA pain and between chemical compounds of angelica sinensis and targets of OA pain showed that the number of active ingredients in ligusticum chuanxiong and angelica sinensis were 26 and 15 repectively, and the active ingredients were mainly phthalides. There was no statistical difference between the 2 Chinese drugs in the degree, betweenness centrality, closest distance centrality and topological coefficient of network of interaction between chemical compounds and targets of OA pain （X2 = 6. 422,P = 0. 491 ;t = -0. 446,P = O. 658 ;t = - 1. 908 ,P =0. 063 ;t = - 1. 205 ,P =0. 234）. There was statistical difference between the 2 Chinese drugs in the average minimal path length of network of interaction between chemical compounds and targets of OA pain （t = 2. 032, P = 0. 048 ）. Conchmiml：The chemical compound contained in ligusticum chuanxiong is similar to that contained in angelica sinensis in chemical spaces and characteristics of interac- tion network to a certain degree, however,ligusticum chuanxiong has more active ingredients than angelica sinensis for treatment of OA pain. The combination of the two drugs has more physico - chemical properties and the two drugs have potential synergistic effect.