Association thermodynamics and conformational stability of beta-sheet amyloid beta(17-42) oligomers: effects of E22Q (Dutch) mutation and charge neutralization.

ABSTRACT: Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Abeta(17-42) oligomers with different protonation states of Glu(22), as well the E22Q (Dutch) mutants. The association free energy of small beta-sheet oligomers shows near-linear trend w

SUBMITTER: Blinov N 

PROVIDER: S-EPMC2808487 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature