Fibril elongation by Aβ(17-42): kinetic network analysis of hybrid-resolution molecular dynamics simulations.

ABSTRACT: A critical step of β-amyloid fibril formation is fibril elongation in which amyloid-β monomers undergo structural transitions to fibrillar structures upon their binding to fibril tips. The atomic detail of the structural transitions remains poorly understood. Computational characterization of the structural transitions is limited so far to short Aβ segments (5-10 aa) owing to the long time scale of Aβ fibril elongation. To overcome the computational time scale limit, we combined a hybrid-resolution model with umbrella sampling and replica exchange molecular dynamics and performed altogether ∼1.3 ms of molecular dynamics simulations of fibril elongation for Aβ17-42. Kinetic network analysis of biased simulations resulted in a kinetic model that encompasses all Aβ segments essential for fibr

SUBMITTER: Han W 

PROVIDER: S-EPMC4156860 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature