论文部分内容阅读
糖原合酶激酶-3α(GSK-3α)是治疗阿尔兹海默症(AD)的关键靶点之一.采用基于R基团的搜索组合分子对接研究了GSK-3α抑制剂的作用特征.以45个马来酰亚胺类GSK-3α抑制剂分子为训练集,采用Topomer CoMFA建立3D-QSAR模型,其拟合与留一法交互验证的复相关系数和标准差分别为r2=0.797,SD=0.210,q2cv=0.611,SDcv=0.280,对22个测试集样本外部预测的复相关系数与标准差分别为r2pred=0.703,SDpred=0.213.以Topomer Search搜索技术设计了25个理论上具有更高活性的新型分子.分子对接对比研究表明,新设计的分子与建模样本同GSK-3α的作用位点具有类似的作用特征,且与对比文献一致.该研究为AD治疗的分子设计与研发提供了新的思路.
Glycogen synthase kinase-3α (GSK-3α) is one of the key targets for the treatment of Alzheimer’s disease (AD). The functional characteristics of GSK-3α inhibitors were investigated using molecular docking based on R group search. Using 45 molecules of maleimide GSK-3α as training set and 3D-QSAR model using Topomer CoMFA, the complex correlation coefficient and standard deviation of the two methods were r2 = 0.797, SD = 0.210, q2cv = 0.611, SDcv = 0.280, the correlation coefficients and standard deviations of external prediction of 22 test samples were r2pred = 0.703 and SDpred = 0.213, respectively. Topology Search technology was used to design 25 theoretically more High activity of new molecules.Material docking studies show that the newly designed molecules and modeling samples with GSK-3α role site has similar characteristics, and consistent with the literature.It is the molecular design and development of AD treatment Provide a new way of thinking.