Modeling the Alzheimer Abeta17-42 fibril architecture: tight intermolecular sheet-sheet association and intramolecular hydrated cavities.

ABSTRACT: We investigate Abeta(17-42) protofibril structures in solution using molecular dynamics simulations. Recently, NMR and computations modeled the Abeta protofibril as a longitudinal stack of U-shaped molecules, creating an in-parallel beta-sheet and loop spine. Here we study the molecular architecture of the fibril formed by spine-spine association. We model in-register intermolecular beta-sheet-beta-sheet associations and study the consequences of Alzheimer's mutations (E22G, E22Q, E22K, and M35A) on the organization. We assess the structural stability and association force of Abeta oligomers with different sheet-sheet interfaces. Double-layered oligomers associating through the C-terminal-C-terminal interface are energetically more favorable than those with the N-terminal-N-terminal interf

SUBMITTER: Zheng J 

PROVIDER: S-EPMC2025669 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature