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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:1519  下载量:150
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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