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

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。

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

To analyze the QSAR of 20 4T Nucleoside analogues, the MM geometry optimization and AMI 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=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 (R2= 0. 771) ,which shows the estimation stability and prediction of the model based on the quantum chemical indexes.