化学学报 ›› 2006, Vol. 64 ›› Issue (9): 949-952. 上一篇    下一篇

研究论文

HLA-A*0201限制性CTL表位定量结构与活性研究

梅虎1,2,周原1,廖志华3,李志良*,1,2   

  1. (1重庆大学化学化工学院 2生物医学工程教育部与重庆市重点实验室 重庆 400044)
    (3西南师范大学生命科学学院 重庆 400715)
  • 收稿日期:2004-12-08 修回日期:2006-01-19 出版日期:2006-05-15 发布日期:2006-05-15
  • 通讯作者: 李志良

Study on Quantitative Structure-Activity Relationships of HLA-A*0201 Restrictive CTL Epitopes

MEI Hu1,2, ZHOU Yuan1, LIAO Zhi-Hua3, LI Zhi-Liang*,1,2   

  1. (1 College of Chemistry and Chemical Engineering, Chongqing University, 2 Key Laboratory of Biomedical Engineering of Both Ministry of Education of China and Chongqing City, Chongqing 400044)
    (3 School of Life Sciences, Southwest Normal University, Chongqing 400715)
  • Received:2004-12-08 Revised:2006-01-19 Online:2006-05-15 Published:2006-05-15
  • Contact: LI Zhi-Liang

采用VHSE氨基酸结构描述子表征HLA-A*0201限制性表位结构, 以遗传算法和偏最小二乘相结合(GA-PLS)对102个训练集进行定量构效关系建模. 剔除3个异常样本后, 据候选模型交互检验及50个外部测试集预测结果, 筛选得到最优偏最小二乘模型(A=2), 其R2, Q2和 分别为0.755, 0.621和0.680. 构效研究显示: CTL表位活性主要与1, 2, 7, 8, 9位氨基酸残基疏水、1, 2位立体及6位残基电性等性质密切相关.

关键词: 细胞毒T细胞, 表位, 定量构效关系, 遗传算法, 偏最小二乘

VHSE descriptors were employed by using GA-PLS to establish QSAR models of 102 HLA-A*0201 restrictive CTL epitopes for major histocompatibility complex or human leukocytoantigen. After removing 3 outliers, total 99 samples were finally used to develop QSAR models. According to the results of cross-validation and those of external validation on 50 test samples, an optimal PLS model (A=2) was derived whose R2, Q2 (leave one out) and were 0.755, 0.621 and 0.680 respectively. From the results of QSAR studies, it can be seen that hydrophobic properties at positions 1, 2, 7, 8 and 9, steric properties at positions 1 and 2 together with electronic properties at positions 4 and 6, were close related to the binding affinities of CTL epitopes.

Key words: cytotoxic T lymphocyte, epitope, quantitative structure-activity relationship, genetic algorithm, partial least squares