In silico design novel (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine derivatives as inhibitors for glycogen synthase kinase 3 based on 3D-QSAR, molecular docking and molecular dynamics simulation.

In silico design novel (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine derivatives as inhibitors for glycogen synthase kinase 3 based on 3D-QSAR, molecular docking and molecular dynamics simulation. Comput Biol Chem. 2020 Jul 04;88:107328 Authors: He Q, Han C, Li G, Guo H, Wang Y, Hu Y, Lin Z, Wang Y Abstract Glycogen Synthase Kinase 3 (GSK-3) is a member of cellular kinase with various functions, such as glucose regulation, cellular differentiation, neuronal function and cell apoptosis. It has been proved as an important therapeutic target in type 2 diabetes mellitus and Alzheimer's disease. To better understand their structure-activity relationships and mechanism of action, an integrated computational study, including three dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, and molecular dynamics (MD), was performed on 79 (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine GSK-3 inhibitors. In this paper, we constructed 3D-QSAR using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) method. The results showed that the CoMFA model (q2 = 0.743,  r2 = 0.980) and the CoMSIA model (q2 = 0.813,  r2 = 0.976) had stable and reliable predictive ability. The electrostatic and H-bond donor fields play important roles in the models. The contour maps of the model visually showed the relationship b...
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Tags: Comput Biol Chem Source Type: research