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化学学报
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化学学报 ›› 2006, Vol. 64 ›› Issue (20): 2065-2070. 上一篇    下一篇

研究论文

基于定量序效模型的计算机辅助虚拟疫苗库设计

周鹏1,2, 李志良*,1,2, 田菲菲1, 张梦军3   

  1. (1重庆大学化学化工学院 重庆 400044)
    (2化学生物传感与计量学国家重点实验室 长沙 410082)
    (3第三军医大学医学检验系 重庆 400040)
  • 投稿日期:2006-03-10 修回日期:2006-05-19 发布日期:2006-10-28
  • 通讯作者: 李志良

QSAM-based Computer-aided Virtual Vaccine Library Design

ZHOU Peng1,2; LI Zhi-Liang*,1,2; TIAN Fei-Fei1; ZHANG Meng-Jun3   

  1. (1 College of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044)
    (2 State Key Laboratory of Chemo/Biosensing and Chemometrics, Changsha 410082)
    (3 Department of Medical Analysis, Third Military Medical University, Chongqing 400040)
  • Received:2006-03-10 Revised:2006-05-19 Published:2006-10-28
  • Contact: LI Zhi-Liang

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给出了基于定量序效模型(QSAM)的计算机辅助虚拟疫苗库设计方案, 并以此为基础成功组建了一个合理规模的HLA-A*0201限制性CTL表位库, 其实现流程如下: (1)从天然氨基酸516种理化性质经主成分分析(PCA)得到一种新的氨基酸描述子: 氨基酸综合性质得分(SP-score); (2)基于SP-score结合遗传-偏最小二乘(GA-PLS)技术建立QSAM模型; (3)利用QSAM模型作为评价工具采用遗传算法(GA)优化CTL表位种群; (4)统计优秀种群中20种氨基酸分别在抗原肽序列不同位置出现频率f; (5)保留f＞F (F为平均出现概率, 对于任意氨基酸为1/20)的氨基酸作为该位置的有利残基类型参与虚拟组合库的构建.

关键词: 定量序效模型, 虚拟疫苗库, HLA-A*0201分子, CTL表位, 遗传算法

Upon QSAM-based virtual vaccine library project, a reasonable human leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocyte (CTL) epitope library was designed. The process is as follows: (a) synthetical property score (SP-score) of amino acids is derived from 516 physicochemical properties by principal component analysis (PCA); (b) based on the SP-score, genetic algorithm-partial least square regression (GA-PLS) is used to construct the quantitative sequence-activity model (QSAM); (c) em-ploying QSAM as evaluation tool, CTL epitopes are optimized by GA; (d) frequency (f) of each amino acid in different position of excellent antigen peptides is calculated; (e) the amino acid in condi-tion of f＞F (F is the random probability, of 1/20 for the natural amino acid) is re-served to be favorable residue type at this position and a structural element of the combinatorial library.

Key words: quantitative sequence-activity model, virtual vaccine library, HLA-A*0201, CTL epitope, genetic algorithm