一株抗JEV单抗可变区的计算机建模及其与JEVE蛋白的分子对接

发布时间：2018-01-13 20:03

  本文关键词：一株抗JEV单抗可变区的计算机建模及其与JEVE蛋白的分子对接　出处：《中国病原生物学杂志》2015年04期 　论文类型：期刊论文

  更多相关文章： 日本脑炎病毒 E蛋白 单克隆抗体 可变区 计算机建模 分子对接

【摘要】：目的利用计算机建模获得单克隆抗体2F2可变区三维结构,再与日本脑炎病毒(JEV)E蛋白进行模拟分子对接,了解JEV E蛋白上与2F2作用的关键氨基酸位点,为阐明2F2的中和作用机制奠定基础。方法利用BLASTP软件在蛋白质数据库(PDB)中搜索2F2同源蛋白。以同源蛋白为模板,用Modeller软件对2F2可变区主链、侧链进行建模,组装出完整的2F2可变区三维结构模型并进行一系列分子动力学优化,得到能量最低的单抗可变区三维结构。最后利用Discovery Studio软件模拟2F2可变区与JEV E蛋白的分子对接。结果获得2F2可变区三维结构模型。模拟分子对接结果显示JEV E蛋白上与2F2可变区相互接触、作用的氨基酸位点有9个,即Ⅰ区的13位谷氨酸、16位丝氨酸、37位天冬氨酸和300位苏氨酸,Ⅲ区的336位赖氨酸、347位天冬氨酸、354位亮氨酸、387位精氨酸和388位甘氨酸残基。其中Ⅰ区13位谷氨酸、16位丝氨酸和37位天冬氨酸可能是中和表位必需的氨基酸。Ⅲ区的387位精氨酸和388位甘氨酸位于优势中和抗原表位区域,336位赖氨酸与已报道的337位中和表位非常接近。结论通过计算机建模确定JEV E蛋白上有9个与单克隆抗体2F2作用的主要氨基酸位点,为利用E蛋白突变体阐明2F2单抗的中和机制提供了依据。
[Abstract]:Objective to obtain the three-dimensional structure of monoclonal antibody 2F2 variable region by computer modeling and then docking with Japanese encephalitis virus (JEV) E protein. Objective: to understand the key amino acid sites of JEV E protein interacting with 2F2. Methods BLASTP software was used to search 2F2 homologous protein in protein database. The homologous protein was used as template. The main chain and side chain of 2F2 variable region were modeled by Modeller software. The complete 3D structure model of 2F2 variable region was assembled and a series of molecular dynamics optimization was carried out. Three-dimensional structure of variable region with the lowest energy was obtained. Finally, 2F2 variable region and JEV were simulated by Discovery Studio software. The molecular docking of E protein. The 3D structural model of 2F2 variable region was obtained. The simulated molecular docking results showed that the JEV E protein was in contact with the 2F2 variable region. There were 9 amino acid sites, namely, aspartic acid at 13 sites and threonine at 300 and aspartic acid at 336lysine in region 鈪，

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