Multifunnel Energy Landscapes for Phosphorylated Translation Repressor 4E-BP2 and Its Mutants.

ABSTRACT: Upon phosphorylation of specific sites, eukaryotic translation initiation factor 4E (eIF4E) binding protein 2 (4E-BP2) undergoes a fundamental structural transformation from a disordered state to a four-stranded β-sheet, leading to decreased binding affinity for its partner. This change reflects the significant effects of phosphate groups on the underlying energy landscapes of proteins. In this study, we combine high-temperature molecular dynamics simulations and discrete path sampling to construct energy landscapes for a doubly phosphorylated 4E-BP2_18-62 and two mutants (a single site mutant D33K and a double mutant Y54A/L59A). The potential and free energy landscapes for these three systems are multifunneled with the folded state and several alternative states lying close in e

SUBMITTER: Kang W 

PROVIDER: S-EPMC7462351 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature