Integrating Machine Learning-Based Virtual Screening With Multiple Protein Structures and Bio-Assay Evaluation for Discovery of Novel GSK3β Inhibitors.

ABSTRACT: Glycogen synthase kinase-3β (GSK3β) is associated with various key biological processes, and it has been considered as a critical therapeutic target for the treatment of many diseases. However, it is a big challenge to develop ATP-competition GSK3β inhibitors because of the high sequence homology with other kinases. In this work, a novel parallel virtual screening strategy based on multiple GSK3β protein structures, integrating molecular docking, complex-based pharmacophore, and naive Bayesian classification, was developed to screen a large chemical database, the 50 compounds with top-scores then underwent a luminescent kinase assay, which led to the discovery of two GSK3β inhibitor hits. The high screening enrichment rate indicates the reliability and practicability of the integrated prot

SUBMITTER: Zhu J 

PROVIDER: S-EPMC7517831 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature