Elucidating Important Sites and the Mechanism for Amyloid Fibril Formation by Coarse-Grained Molecular Dynamics.

ABSTRACT: Fibrils formed by the β-amyloid (Aβ) peptide play a central role in the development of Alzheimer's disease. In this study, the principles governing their growth and stability are investigated by analyzing canonical and replica-exchange molecular dynamics trajectories of Aβ_(9-40) fibrils. In particular, an unstructured monomer was allowed to interact freely with an Aβ fibril template. Trajectories were generated with the coarse-grained united-residue force field, and one- and two-dimensional free-energy landscapes (FELs) along the backbone virtual-bond angle θ and backbone virtual-bond-dihedral angle γ of each residue and principal components, respectively, were analyzed. Also, thermal unbinding (unfolding) of an Aβ peptide from the fibril template was investigated. These analyse

SUBMITTER: Rojas A 

PROVIDER: S-EPMC5245180 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature