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基于分子对接虚拟筛选中药丹参中的MDM2靶向抑制活性成分
发表时间：2017-12-15 浏览量：2197 下载量：286
| 全部作者： | 刘军锋，姚云峰，昝俊峰，李辉，陈仕红，陈林霖，常聪 |
| 作者单位： | 湖北中医药大学中药资源与中药复方教育部重点实验室；老年病中药新产品湖北省协同创新中心；湖北中医药大学药学院 |
| 摘 要： | 目的：在中医药理论的指导下，利用分子对接虚拟筛选技术从活血化瘀类中药丹参中发现MDM2-p53蛋白相互作用抑制活性成分。方法：利用三维分子药物辅助设计软件PyRx的Vina模块，以MDM2蛋白（PDB ID：5TRF）为受体，对丹参中的小分子化合物进行虚拟筛选，并以MDM2-p53蛋白相互作用的高活性抑制剂Nutlin-3为对照，发现MDM2靶向抑制活性成分。结果：从丹参已探明的202种成分中，共发现二氢丹参酮Ⅰ、二氢丹参内酯、丹参螺缩酮内酯、丹参新醌d和次甲丹参醌5个单体化合物能够与MDM2蛋白形成较稳定的复合物，可能成为MDM2抑制剂的小分子化合物。结论：本研究通过将现代计算机虚拟筛选技术与传统中医药理论结合，发现了活血化瘀类中药丹参在MDM2-p53蛋白相互作用位点的抗肿瘤活性成分，有助于阐释其可能存在的抗肿瘤药效物质基础与作用机理。 |
| 关 键 词： | 中药学其他学科；活性成分；虚拟筛选；分子对接；丹参；MDM2-p53蛋白相互作用 |
| Title： | Identify active components as MDM2 antagonists from Radix Salviae based on molecular docking-based virtual screening |
| Author： | LIU Junfeng, YAO Yunfeng, ZAN Junfeng, LI Hui, CHEN Shihong, CHEN Linlin, CHANG Cong |
| Organization： | Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine; New Products of TCM Senile Diseases Co-Innovation Center of Hubei; College of Pharmacy, Hubei University of Chinese Medicine |
| Abstract： | Objective: According to traditional Chinese medical principles, we attempted to identify MDM2-p53 protein-protein interaction antagonists from herbal medicine Danshen (Radix Salviae) of blood-activating and stasis-resolving using molecular docking-based virtual screening techniques. Methods: A structure-based pharmacophore search and docking simulation were carried out targeting MDM2 protein (PDB ID: 5TRF) using Vina modular of PyRx to filter small molecule compounds in Danshen. And then novel scaffolds inhibiting MDM2-p53 protein-protein interaction were found using potent MDM2-p53 protein-protein interaction antagonist Nutlin-3 as control. Results: Among the 202 proven constituents of Danshen, 5 compounds, dihydrotanshinone I, dihydrotanshinlactone, danshenspiroketallactone, dan-shexinkum d and methylenetanshinquinone could form more stable compound with MDM2 protein, which were identified as potential MDM2 antagonists. Conclusion: In this paper, computer aided molecular virtual docking technology was combined with traditional Chinese medicine theory to explore and identify anti-cancer active compounds in Danshen targeting MDM2-p53 protein-protein interaction. It helps to explain the chemical material basis and mechanisms of anti-tumor efficacy of herbal medicine Danshen. |
| Key words： | other subjects of traditional Chinese pharmacology; active constituent; virtual screening; molecular docking; Radix Salviae; MDM2-p53 protein-protein interaction |
| 发表期数： | 2017年12月第23期 |
| 引用格式： | 刘军锋，姚云峰，昝俊峰，等. 基于分子对接虚拟筛选中药丹参中的MDM2靶向抑制活性成分[J]. 中国科技论文在线精品论文，2017，10（23）：2649-2654. |
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