分子模拟用于HLA-A2.1限制性CTL表位的高通量筛选  

The Application of Molecular Modeling in High Flux Screening of HLA-A2.1 Restricted CTL Epitopes

作　　者：林治华[1] 全学军[1] 周跃钢[1] 

机构地区：[1]重庆工学院生物工程学院,重庆400050

出　　处：《重庆工学院学报》2003年第2期6-9,共4页Journal of Chongqing Institute of Technology

摘　　要：应用SiliconGraphics图像工作站及InsightⅡ软件,分别建立MART 1的6个CTL预测表位与HLA A2.1结合的三维结构,并进行分子动力学模拟,通过对各结合特征性参数的计算,对各表位肽与HLA A2.1结合稳定性进行了比较。应用Merrifield固相多肽合成技术合成上述小肽,通过HLA A2.1与各肽亲和力分析试验,证实分子模拟结果的可靠性。结果发现通过分子模拟手段计算所得6个表位与HLA A2.1结合特性结果,基本与通过实验手段所得结果相符。故计算机分子模拟在CTL表位与MHC Ⅰ类分子的亲合力研究中,具有简单、直观、快速、准确等优点,该方法在筛选MHC Ⅰ类分子高亲合性CTL表位的研究中具有诱人的应用前景。Using Silicon Graphics workstation and Insight II software, this paper builds the threedimensional structure of 6 CTL epitope candidates bound to the HLAA2.1 molecule, carries out dynamic molecular simulation and compares binding stabilities of all the epitope peptides by computing all the parameters related to binding affinity. To verify the reliability of the results obtained from molecule modeling, this paper uses Merriefied solidoid multipeptide synthesizing technology to synthesize the above peptides and carries out binding affinity tests between HLAA2.1 and all the peptides. The results obtained from molecular modeling are consistent with those from the MHC peptide binding affinity assays in substance. Therefore, this study demonstrates that molecular modeling can be used in selecting CTL epitope candidates with high affinities of MHCI molecules because of its convenience, speediness and veracity.

关 键 词：分子动力学模拟 MART-1 三维结构 CTL表位 HLA-A2.1 肽 亲和力 MHC-I类分子 细腻毒性T细腻 肿瘤特异性免疫治疗 抗原 

分 类 号：R730.5[医药卫生—肿瘤] R392[医药卫生—临床医学]