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Updated: Feb 12, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Exploring the interactions of EGFR with phosphorylated Mig6 by molecular dynamics simulations and MM-PBSA
1Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, Changchun 130023, People's Republic of China.
Abstract:
Mig6, a negative regulator, directly binds to epidermal growth factor receptor (EGFR), including Mig6-segment1 and Mig6-segment2. Mig6 requires phosphorylation of Y394 on Mig6-segment2 in order to inhibit EGFR. Two phosphorylation pathways for Y394 have been previously reported and the first way may phosphorylate Y394 primed by Y395 phosphorylation. Besides, the binding mechanism of phosphorylated Mig6-segment2 with EGFR has not been elucidated clearly. Focused on EGFR complex with phosphorylated Mig6-segment2, molecular dynamics (MD) simulations were performed to explore the interactions of Mig6-segment2 with EGFR. Our results indicate a probable phosphorylation pathway on Y394 and some key residues of EGFR play important roles in binding to phosphorylated Mig6-segment2. In addition, a special L-shaped structure was found to be possibly associated with irreversible inhibition of EGFR by Mig6. Our work can give meaningful information to better understand the phosphorylation pathways for Y394 and the interactions of EGFR binding to phosphorylated Mig6-segment2.
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