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Article

E76K Mutation Promotes SHP2 Activation by Rewiring Allosteric Networks That Drives Conformational Transitions.

Journal of chemical information and modeling - 22 Sept 2025

Zhao Derui, Liu Mengting, Duan Hui, Zhu Junyao, Yang Liquan, Sang Peng

Abstract excerpt

The E76K mutation in protein tyrosine phosphatase (PTP) SHP2 is a recurrent driver of developmental disorders and cancers, yet the mechanism by which this single-site substitution promotes persistent activation remains elusive. Here, we combine path-based conformational sampling, unbiased molecular dynamics (MD) simulations, Markov state models (MSMs), and neural relational inference (NRI) to elucidate how E76K...

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PMID: 40920905
DOI: 10.1021/acs.jcim.5c01201

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