应用量化参数研究d4T核苷酸类似物的结构与抗HIV-1活性的相关性  

Structural characterization of d4T nucleoside analogues through quantum chemical indexes and anti-HIV activity prediction by QSAR

作　　者：林红卫[1] 赵军[1] 毛新平[1] 李银辉[1] 李志良[2] 

机构地区：[1]怀化学院化学系,湖南怀化418008 [2]重庆大学化学化工学院,重庆400044

出　　处：《计算机与应用化学》2007年第4期536-538,共3页Computers and Applied Chemistry

基　　金：湖南省教育厅资助课题(04C454)

摘　　要：应用MM+分子力学法、量子化学AM1法计算了20个d4T核苷酸类似物的优势构象和电子结构,并用逐步回归分析方法寻找其量化指数与抗HIV(艾滋病)活性的关系。结果表明:1)d4T核苷酸类似物的油水分配系数LogP与活性参数间呈较好的抛物线关系,LogP处于0．95-2．45区间是d4T核苷酸类似物具有良好抗HIV活性的重要条件。2)建立了量化指数与活性之间的定量模型,取得了良好的结果,其模型相关系数为R=0．948;继以留一法(Leave-one-out,LOO)进行交互检验,复相关系数为R2C(?)=0．771,说明定量相关模型具有良好的稳定性和预测能力。To analyze the QSAR of 20 4T Nucleoside analogues, the MM^＋ geometry optimization and AM1 quantum chemical indexes had been performed. It can be concluded as follows： （ 1 ） The relationship between LogP values and activities of 4T Nucleoside analogues is parabola. The LogP values of the high active 4T Nucleoside analogues must be 0. 95 to 2.45. （2） A reasonable molecular modeling equation was achieved with a quite high correlation coefficient（ R^2 = 0. 948 ） by a stepwise multiple regression （SMR） for the prediction of the anti-HIV activity. The performance of the model was tested through cross-validation by the leave-one-out procedure （LOO） and satisfactory results were obtained （Re = 0. 771 ） ,which shows the estimation stability and prediction of the model based on the quantum chemical indexes.

关 键 词：MM^+ AM1 d4T核苷酸类似物 定量结构活性相关 

分 类 号：O641.12[理学—物理化学]