Study on SHP2 Conformational Transition and Structural Characterization of Its High-Potency Allosteric Inhibitors by Molecular Dynamics Simulations Combined with Machine Learning.

ABSTRACT: The src-homology 2 domain-containing phosphatase 2 (SHP2) is a human cytoplasmic protein tyrosine phosphatase that plays a crucial role in cellular signal transduction. Aberrant activation and mutations of SHP2 are associated with tumor growth and immune suppression, thus making it a potential target for cancer therapy. Initially, researchers sought to develop inhibitors targeting SHP2's catalytic site (protein tyrosine phosphatase domain, PTP). Due to limitations such as conservativeness and poor membrane permeability, SHP2 was once considered a challenging drug target. Nevertheless, with the in-depth investigations into the conformational switch mechanism from SHP2's inactive to active state and the emergence of various SHP2 allosteric inhibitors, new hope has been brought to this target

SUBMITTER: Wujieti B 

PROVIDER: S-EPMC11721961 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature