Molecular Dynamics Simulations in Designing DARPins as Phosphorylation-Specific Protein Binders of ERK2.

ABSTRACT: Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play key roles in promoting cell survival and proliferation through the phosphorylation of various substrates. Remarkable antitumour activity is found in many inhibitors that act upstream of the ERK pathway. However, drug-resistant tumour cells invariably emerge after their use due to the reactivation of ERK1/2 signalling. ERK1/2 inhibitors have shown clinical efficacy as a therapeutic strategy for the treatment of tumours with mitogen-activated protein kinase (MAPK) upstream target mutations. These inhibitors may be used as a possible strategy to overcome acquired resistance to MAPK inhibitors. Here, we report a class of repeat proteins-designed ankyrin repeat protein (DARPin) macromolecules targeting ERK2 as inhibitors. The structur

SUBMITTER: Gautam V 

PROVIDER: S-EPMC8347146 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature