Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach.

ABSTRACT: γ-Secretase is an intramembrane-cleaving aspartyl protease that plays an essential role in the processing of a variety of integral membrane proteins. Its role in the ultimate cleavage step in the processing of amyloid precursor protein to form amyloid-β (Aβ) peptide makes it an important therapeutic target in Alzheimer's disease research. Significant recent advances have been made in structural studies of this critical membrane protein complex. However, details of the mechanism of activation of the enzyme complex remain unclear. Using a multiscale computational modeling approach, combining multiple coarse-grained microsecond dynamic trajectories with all-atom models, the structure and two conformational states of the γ-secretase complex were evaluated. The transition between enzymatic stat

SUBMITTER: Aguayo-Ortiz R 

PROVIDER: S-EPMC5618787 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature