CAJ | 학술논문

通过分子对接和三维定量构效关系(3D-QSAR)两种方法来确定两类马来酰胺类的糖原合成酶激酶-3β(GSK-3β)抑制剂的结合方式.首先,用分子对接确定抑制剂与GSK-3β的结合模式及其相互作用;然后用比较分子力场分析法(CoMFA)与比较分子相似性指数分析法(CoMSIA)对48个化合物做三维定量构效关系的分析.两种方法得出的交互验证回归系数分别为0.669(CoMFA)和0.683(CoMSIA),证明该模型具有很好的统计相关性,同时也说明该模型具有较高的预测能力.根据该模型提供的信息,设计出9个预测性较好的分子.
통과분자대접화삼유정량구효관계(3D-QSAR)량충방법래학정량류마래선알류적당원합성매격매-3β(GSK-3β)억제제적결합방식.수선,용분자대접학정억제제여GSK-3β적결합모식급기상호작용;연후용비교분자력장분석법(CoMFA)여비교분자상사성지수분석법(CoMSIA)대48개화합물주삼유정량구효관계적분석.량충방법득출적교호험증회귀계수분별위0.669(CoMFA)화0.683(CoMSIA),증명해모형구유흔호적통계상관성,동시야설명해모형구유교고적예측능력.근거해모형제공적신식,설계출9개예측성교호적분자.
Molecular docking and three-dimensional quantitative structure-activity relationship(3D-QSAR)approaches were used to characterize the binding features of two different series of maleimide glycogen synthase kinase-3β(GSK-3β)inhibitors,3-(indol-3-yl)-4-(1H-indazol-3-yl)maleimides and 3-(benzofuran-3-yl)-4-(indol-3-yl)maleimides.First,molecular docking was applied to characterize the binding modes and interactions between ligands and GSK-3β.A comparative molecular field analysis(CoMFA)and comparative molecular similarity indice analysis (CoMSIA)were then employed to develop 3D-QSAR models of 48 compounds.The excellent predictive capability of these 3D-QSAR models were validated by a satisfactory correlation coefficient using leave-one-out cross-validation q2 values(q2 values were 0.669 and 0.683 for CoMFA and CoMSIA,respectively).Satisfactory predictions on externally tested compounds also validated the models.Using the 3D-QSAR models,9 molecules were designed with predicted good binding affinities in terms of molecular docking score and they also had good predicted values for inhibition.