HLA-A2限制性CTL表位肽定量构效关系研究

基于SCORE打分函数，运用定量构效关系的理论和方法研究了HLA—A2限制性CTL表位九肽结构与亲和性间的定量关系，并建立了SCORE得分与亲和性的定量关系模型，并用外部样本（5个HLA—A2限制性CTL表位九肽）作为预测集用于检验模型的预测能力．基于SCORE打分函数建立的定量模型具有较好的相关性（r=0，9165，RMS=0．38）和对外部样本的预测能力（rpred=0．9847，RMS=0．135）．基于SCORE打分函数，运用定量构效关系研究的理论和方法建立了HLA—A2限制性CTL表位亲和性的定量预测方法，为实验鉴定高亲和性HLA—A2限制性CTL表位提供了理论依据．     

QSAR analysis of substituted benzylamino- and heterocyclylmethylamino-carbodithioate derivatives of 4-（3H）-quinazolinone using CoMFA and SCORE2.0

Thymidylate synthase (TS) is a critical enzyme for DNA biosynthesis and many nonclassical lipophilic antifolates targeting this enzyme are quite efficient and encouraging as antitumor drugs. In this paper, the binding model of 14 antifolates of substituted benzylamino- and heterocyclylmethylamino- carbodithioate derivatives of 4-(3H)-quinazolinone with TS is examined using molecular simulation methods―― FlexiDock and SCORE2.0. The resulting conformation and orientation of these antifolates are directly applied to CoMFA study. The robust QSAR model, its three-dimensional contour map, and binding score of these antifolates derived from SCORE2.0 provide guidelines for structural optimiza- tion of current antifolates. The experiment indicates that deletion of cancer chemopreventive structure of dithiocarbamate is unfavorable for interaction between TS and antifolates.