人3型腺病毒六邻体塔区分子动力学模拟与抗原性分析 精灵论文.doc

人 3 型腺病毒六邻体塔区分子动力学模拟与 抗原性分析 袁晓辉1,3，王迎晨1，曲章义1，高虹1，商蕾1，吴晓敏2 （1. 哈尔滨医科大学公共卫生学院卫生微生物学教研室，哈尔滨 150081； 5 2. 东北林业大学森林植物生态学教育部重点实验室，哈尔滨 150040； 3. 中国医学科学院北京协和医学院病原生物学研究所，北京 100730） 摘要：目的：探索腺病毒六邻体的抗原表位是构象性还是线性为主。方法：基于本实验室分 离到的人 3 型腺病毒毒株 Harbin04B 的六邻体序列，对人 3 型腺病毒六邻体三聚体的塔区进 行同源建模和长程分子动力学模拟。结果：构建了人 3 型腺病毒六邻体三维结构模型，分子 10 动力学模拟表明其塔区内不存在稳定的构象性表位。结论：人 3 型腺病毒六邻体塔区是其主 要中和表位所在区域，该区域不存在稳定的构象性表位，而是以线性表位为主。 关键词：病医学微生物学；人腺病毒；六邻体；同源建模；原核表达；抗原性 中图分类号：O641；R373.1 15 The Molecular Dynamic Simulation and Antigenicity Analysis of the Tower Region of Human Adenovirus Type 3 Hexon YUAN Xiaohui1,3, WANG Yingchen1, QU Zhangyi1, GAO Hong1, SHANG Lei1, WU Xiaomin2 20 (1. Department of Hygienic Microbiology, Public Health College, Harbin Medical University, Harbin 150081; 2. Key Laboratory of Forest Plant Ecology, Ministry of Education，Northeast Forestry University， Harbin 150040; 3. Institute of Pathogen Biology, Chinese Academy of Medical Sciences Peking Union Medical 25 College, Beijing 100730) Abstract: Objective: To explore whether the antigen epitopes of adenovirus hexon is linear or comformational. Method: A three-dimensional model of the HAdV3 hexon was obtained by homology modeling based on the completed hexon amino acid sequence of HAdV3 isolated strain Harbin04B. MD simulation were employed to study the dynamics conformation of the hexon tower region (the total 30 epitopes composition of hexon). Result: A three-dimensional model of the HAdV3 hexon was obtained and refined. MD simulation shows that there is no stable conformational epitope in the tower region of HAdV3 hexon. Conclusion: The major neutralization epitiopes of HAdV3 was located in its tower region, which hosts linear epitopes rather than conformational epitopes. Keywords:medical microbiology; human adenovirus; hexon; homology modeling; prokaryotic 35 expression; antigenicity 0 引言 人腺病毒（Human Adenovirus，HAdV）是引起人类呼吸道和消化道等部位感染的重要 病原之一，迄今为止已经发现 55 个人腺病毒血清型[1]。腺病毒六邻体（Hexon）是腺病毒的 40 主要结构蛋白，可以刺激机体产生型特异性的中和抗体[2]。抗原中能被 B 细