Methionine Oxidation Changes the Mechanism of Aβ Peptide Binding to the DMPC Bilayer.

ABSTRACT: Using all-atom explicit solvent replica exchange molecular dynamics simulations with solute tempering, we study the effect of methionine oxidation on Aβ10-40 peptide binding to the zwitterionic DMPC bilayer. By comparing oxidized and reduced peptides, we identified changes in the binding mechanism caused by this modification. First, Met35 oxidation unravels C-terminal helix in the bound peptides. Second, oxidation destabilizes intrapeptide interactions and expands bound peptides. We explain these outcomes by the loss of amphiphilic character of the C-terminal helix due to oxidation. Third, oxidation "polarizes" Aβ binding to the DMPC bilayer by strengthening the interactions of the C-terminus with lipids while largely releasing the rest of the peptide from bilayer. Fourth, in contrast to t

SUBMITTER: Lockhart C 

PROVIDER: S-EPMC6459879 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature