HLA-A^＊0201限制性CTL表位肽分子力场分析

Molecular Field Analysis on HLA-A^＊ 0201 Restricted CTL Epitope

运用比较相似性指数分析(CoMISA)方法研究了203个HLA-A*0201限制性CTL表位九肽结构与亲和性间的关系,另外30个表位九肽作为预测集用于检验模型的预测能力.得到构效关系模型结果q2=0.548,r2=0.963,F=553.4,SD=0.154.在CoMSIA计算中,当引入疏水场时,三维构效关系模型能得到明显改善.通过该三维构效关系模型,可较精确地估算预测集中30个CTL表位肽与HLA-A*0201间的亲和力(r2pred=0.532,SD=0.454).通过分析分子场等值面图在空间的分布,可以观察到表位肽分子周围的立体及疏水特征对表位肽H与A-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.

Using comparative molecular similarity indices analysis （CoMSIA）, this paper studies relationship between the structure and affinity of a set of 203 restricted CTL peptides, and uses another 30 peptides as predictive set to determine the predictive value of test models, resulted in structure-activity relationship model is q^2 = 0. 548 and r^2 pred = 0.532. When hydrophobic field is introduced into CoMSIA calculation, 3- dimensional structure-activity. Relationship model can be improved considerably. According to the model, the affinity between the 30 CTL peptides in the predictive set and HLA-A^＊ 0201 can be exactly estimated （ rpred^2 = 0.532, SD = 0.454）. By analyzing the spatial distribution of surface chart of isoline, the effect of the 3-D and hydrophobic characteristics of eptode on epitode H and HLA-A^＊ 0201 can be observed, which provides theoretical basis for further structural transformation of CTL peptides and the molecular design for therapeutic vaccine.