摘要
运用比较分子力场(CoMFA)和比较相似性指数分析(CoMSIA)方法研究了50个HLA-A* 0201限制性CTL表位九肽结构与亲和性间的关系,另外15个表位九肽作为预测集用于检验模型的预测能力。结果表明,采用CoMSIA得到的构效关系模型(q2 =0.608,r2 =0.987,F=440.4,SD=0. 111)要明显优于采用CoMFA得到的构效关系模型。在CoMSIA计算中,当引入疏水场时,三维构效关系模型得到明显改善,通过该三维构效关系模型,可较精确地估算预测集中15个CTL表位肽与HLA-A* 0201间的亲和力(r2pred=0. 703,SD=0. 368)。通过分析分子场等势面图在空间的分布,可以观察到表位肽分子周围的立体及疏水特征对表位肽与HLA-A* 0201间结合亲和力的影响,从而为进一步对CTL表位肽进行结构改造并基于此进行治疗性疫苗分子设计提供理论基础。
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 indices analysis (CoMSIA). A test set of 15 peptides was used to determine the predictive value of the models. The results show that the CoMSIA models are better more than the CoMFA models. The CoMFA models gave q^2 and r^2_(pred) below 0.5. The best CoMSIA model has q2 =0.611 and r2pred= 0.703, and includes hydrophobic steric. 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.
出处
《重庆工商大学学报（自然科学版）》
2005年第2期143-147,193,共6页
Journal of Chongqing Technology and Business University:Natural Science Edition
