How oncogenic mutations activate human MAP kinase 1 (MEK1): a molecular dynamics simulation study.

ABSTRACT: Approximately 30% of all types of human cancers possess a constitutively activated the mitogen-activated protein kinase (MAPK) signaling pathway while MAP kinase 1 (MEK1) is a critical component of this pathway. It has been reported mutations could improve the activity of MEK1 to result in cell proliferation and transformation, which is a known oncogenic event in various cancer types. In this study, eight molecular dynamics simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), combined with protein structure network were performed to explore the mechanism that mutations activate MEK1. Protein structure networks and hydrogen bonds analysis demonstrated that active mutations broke the interaction between activation segments (residues 216-222) and C-helix (residues 105-12

SUBMITTER: Liu Y 

PROVIDER: S-EPMC8177546 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature