5,6-二氢-2-吡喃酮作为HIV-1蛋白酶抑制剂的3D-QSAR和对接研究

摘要

In order to well understand the chemical-biological interactions governing their activities toward HIV-1 protease activity, QSAR model of 24 5,6-dihydro-2-pyrones derivatives with inhibitory HIV-1 is developed.Here a quantitative structure activity relationship (QSAR) model was built by multiple linear regression (MLR) to analyze the estimation stability and prediction ability of both internal and external validations of the model.The correlation coefficient (R2cum) of established MLR model is 0.961, the cross-validated correlation coefficient (Q2CV) of MLR model is 0.897, furthermore, the cross-validated correlation coefficient for the test set (Q2ext) is 0.880 respectively.The binding mode pattern of the compounds to the binding site of protease enzyme was confirmed by docking studies.The information provided by three dimensional QSAR model may lead to better understanding of the structural requirements of 5,6-dihydro-2-pyrones derivatives and help to design novel and potent anti-HIV-1 protease molecules.%本文采用分子对接法研究了24个5,6-二氢-2-吡喃酮衍生物与HIV-1蛋白酶的相互作用,并采用三维定量构效关系(3D-QSAR)研究了药物分子化学结构和生物活性之间的关系.最终得到模型的复相关系数(R2cum)为0.961、 留一法交互校验复相关系数(Q2cv)为0.897,外部交互验证复相关系数(Q2ext)为0.880,从结果可以看出三维定量构效关系对化合物的抗艾滋病活性具有比较好的预测能力.然后通过分子对接研究了配体小分子和HIV-1蛋白酶活性氨基酸残基之间的结合模式,这些信息对于以后设计合成新的抗艾滋病药物具有一定的指导作用.