Theoretical Exploring Selective-Binding Mechanisms of JAK3 by 3D-QSAR, Molecular Dynamics Simulation and Free Energy Calculation.

ABSTRACT: Janus kinase 3 (JAK3) plays a critical role in the JAK/STAT signaling pathway and has become an attractive selective target for the treatment of immune-mediated disorders. Therefore, great efforts have been made for the development of JAK3 inhibitors, but developing selective JAK3 inhibitors remains a great challenge because of the high sequence homology with other kinases. In order to reveal the selective-binding mechanisms of JAK3 and to find the key structural features that refer to specific JAK3 inhibition, a systematic computational method, including 3D-QSAR, molecular dynamics simulation, and free energy calculations, was carried out on a series of JAK3 isoform-selective inhibitors. Necessary pharmacodynamic structures and key residues involved in efficient JAK3-inhibition were then

SUBMITTER: Zhu J 

PROVIDER: S-EPMC7266956 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature