【摘要】 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.更多还原

【Abstract】 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 q2 =0.548 and r2 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(r2pred=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.更多还原