Acta Chimica Sinica ›› 2004, Vol. 62 ›› Issue (18): 1835-1840. Previous Articles     Next Articles

HLA-A*0201限制性CTL表位肽的三维定量构效关系的研究

林治华1, 胡勇1, 吴玉章2   

  1. 1. 重庆工学院生物工程学院, 重庆, 400050;
    2. 第三军医大学免疫研究所, 重庆, 400038
  • 投稿日期:2004-03-23 修回日期:2004-06-07 发布日期:2014-02-17
  • 通讯作者: 林治华,E-mail:zhlincq@sina.com E-mail:zhlincq@sina.com
  • 基金资助:
    国家自然科学基金(Nos.2001CB510001,90208028)、重庆市科委应用基础(No.7973)资助项目.

3D-QSAR Study on the HLA-A*0201 Restricted CTL Epitope

LIN Zhi-Hua1, HU Yong1, WU Yu-Zhang2   

  1. 1. College of Bioengineering, Chongqing Institute of Technology, Chongqing 400050;
    2. Institute of Immunology, The Third Military Medical University, Chongqing 400038
  • Received:2004-03-23 Revised:2004-06-07 Published:2014-02-17

A set of 50 peptides with affinity for the class I MHC HLA-A*0201 molecule was subjected to three-dimensional quantitative structure-affinity relationship (3D QSAR) studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). A test set of 15 peptides was used to determine the predictive potential of the models. The results show that the CoMSIA models are better than the CoMFA models. The CoMFA models gave q2 and r2 pred below 0.5. The best CoMSIA model has q2=0.628 and r2=0.997, and includes hydrophobic and steric fields, which were used to predict the binding affinity of 15 samples in the test set with good result rpred2=0.743. The results show that the hydrophobic interactions play a dominant role in peptide-MHC molecule binding. CoMSIA coefficient contour maps were used to analyze the structural features of the peptides accounting for the affinity in terms of the positively contributing physicochemical properties: local hydrophobicity and steric bulk. The results also provide useful information for structure modification of CTL epitope and theory base for molecular design of therapeutic vaccine.

Key words: cytotoxic T lymphocyte(CTL), epitope, peptide, comparative molecular field analysis, comparative molecular similarity indices analysis