基于氨基酸性质的EB病毒抗原MHC-Ⅰ类分子限制性表位的定量构效关系建模  

Quantitative structure-activity relationship modeling of MHC class-Ⅰ restrained antigenic epitope of Epstein-Barr virus based on the properties of amino acids

作　　者：韩英子[1] 王远强[1] 胡勇[1] 纪永军[1] 路亚阔[1] 蓝君[1] 罗鸿[1] 林治华[1] 

机构地区：[1]重庆理工大学药学与生物工程学院,400054

出　　处：《免疫学杂志》2013年第1期59-63,共5页Immunological Journal

基　　金：国家自然科学基金项目(60873103);国家自然科学基金重点项目(30830090);重庆市自然科学基金(CSTC;2010BB5306)

摘　　要：目的建立EB病毒(EBV)抗原表位的理论计算模型并用于其定量预测,为肿瘤免疫的多肽疫苗设计提供理论基础。方法从表位数据库中收集33条EBV抗原表位,使用逐步回归(STR)方法筛选2个对平衡解离常数(KD)贡献较大的结构参数用于表位的结构表征,最后用多元线性回归(MLR)方法建立结构参数与KD的定量构效关系(QSAR)模型。结果该模型具有较好的稳定性(R2=0.637,Q2=0.581)与预测能力(R2test=0.501)。结论此方法可确定表位中各个氨基酸的物理性质对于平衡解离常数的贡献,为表位设计与改造提供直接线索;STR和MLR相结合建模方法具有物化意义明确、易于解释及操作简便易行等优点。Epstein-Barr virus （-EBV） is highly associated with several neoplastic diseases. The development of vaccine based on the antigenic epitope is very important for immunotherapies of human cancers. It is necessary to construct theoretical model for quantitative prediction of epitope, because the identification and screen of epitope need long time and high cost through experiments. In this study, 33 epitopes from EBV had been collected from epitope database. Then, the properties with significant contribution for equilibrium dissociation constant （KD） were screened by the stepwise, which were used to characterize the epitopes. Finally, the quantitative structure-activity relationship model between structural variables and KD was constructed by multiple linear regressions （MLR）. The QSAR model has good reliability （R^2=0.637, Q2=0.581） and predictive ability （R^2test=0.501）, and can provide more clues for the design and modification of epitope. The QSAR model constructed by STR and MLR has some advantages, such as good reliability and predictive ability, definitive physiochemical meaning and easier operation, and it can guide the rational design and structural modification of epitope directly.

关 键 词：EB病毒 表位 平衡解离常数 构效关系 肿瘤 

分 类 号：R392.9[医药卫生—免疫学]