Using docking to investigate mechanism of action of GSK-3α inhibitors

Glycogen synthase kinase-3α(GSK-3α) is one of the key targets against Alzheimer′s disease(AD).We use R-groups search and molecular docking to investigate mechanism of action of new inhibitors of GSK-3α.A total of 45 3-anilino-4-phenylmaleimide derivatives were used to develop a 3D-QSAR model based on Topomer CoMFA,and 22 test samples were used to validate the predictive ability of the model obtained.The multiple correlation coefficient and the standard deviation of fitting modeling,leave one out cross validation,and external validation were as follows:r2=0.797,SD=0.210,q2cv=0.611,SDcv=0.280,r2pred=0.703,and SDpred=0.213.We design 25 new compounds with high activity in theory using research.Through comparison,the results of molecular docking show that the interaction between new designed molecules and GSK-3α is well agreement with the experimental conclusion of other reports.This study provides a new approach for drug design and development toward AD treatment.