芪苈强心胶囊中强心有效成分及其作用机理的计算机模拟

目的:通过计算机模拟技术研究芪苈强心胶囊中已知结构化合物的分子特征,分析与强心西药分子结构、理化性质相似的中药成分,并寻找比对中西药分子的作用靶点,以期为新药研发或作用机制研究提供思路。方法:通过中西药的分子集构建,进行中西药分子的理化性质分析和结构比对,同时通过反向药效团搜索进行中西药分子的作用靶点结合的探讨。结果:我们利用软件构建了45个中药成分和3个强心类西药成分的平面结构和三维结构,通过分子结构相似度的比较和反向药效团搜索,发现这45个中药分子整体与洋地黄毒苷的相似度最高,同时中药分子中黄芪苷和人参皂苷与各西药分子的结构相似度最高;理化性质对比分析显示,3个强心西药的相对分子质量并不是最大的,然而其表面极性却最大;通过反向药效团搜索发现,这48个小分子中有10个小分子与66个蛋白药效团模型发生了较好的结合,其中西药地高辛只与一个药效团发生接合,而中药有6个成分都与多个药效团发生结合,其中以丹酚酸A结合的药效团最多。结论:与西药仅结合单一蛋白药效团不同,中药分子更易与多个蛋白药效团发生结合,由此推测其作用靶点和作用途径可能更为多样化。

Computational simulation of active ingredients and its mechanism of cardiac effect in Qili Qiangxin capsules

Objective: To research the molecular characteristics of known compounds in Qili Qiangxin capsule by computer simulation, analysis the Traditional Chinese Medicine(TCM) composition which molecular structure and physicochemical property were similar to the cardiotonic western medicine, and to ifnd and compare the targets of the Chinese and Western medicine molecules, so as to provide ideas for the new drug development or mechanism research.Methods: To construct the molecular set of Chinese and Western medicine, so as to analyze the physicochemical property and compare the structure of Chinese and Western medicine molecules, and the combination of the action target of Chinese and Western medicine molecules were probed by the reverse ifnding target.Results:The planar structure and three-dimensional structure of 45 TCM ingredients and 3 cardiac western medicine ingredients were constructed by software. By comparing the similarity of molecular structure and reverse ifnding target, we found that the 45 TCM molecular were most similar to digitoxin as a whole, and the structure of astragalin and ginsenoside among the TCM molecular were most similar to the western medicine molecules. Contrastive analysis of physicochemical properties showed that the molecular weight of the 3 cardiac western medicine was not the biggest, but which polar surface area was the largest. 10 among the 48 small molecules were found to have a good combination with the 66 protein pharmacophore models by the reverse ifnding target. The western medicine digoxin was combined with only one pharmacophore, while 6 components of TCM were combined with multiple pharmacophores, among which salvianolic acid A was associated with the most pharmacophores.Conclusion: Different from western medicines which were combined with only one protein pharmacophore, the TCM molecules were more likely to be combined with multiple protein pharmacophores, thus it can be speculate that the target spot and function pathway of TCM could be more diverse.