Insight into the stability of cross-beta amyloid fibril from molecular dynamics simulation.

Abstract:

:Amyloid fibrils are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases such as Alzheimer's disease, type II diabetes mellitus, the transmissible spongiform encephalopathies, and prion disease. The mechanism of fibril formation is still hotly debated and remains an important open question. In this study, we utilized molecular dynamics (MD) simulation to analyze the stability of hexamer for eight class peptides. The MD results suggest that VEALYL and MVGGVV-1 are the most stable ones, then SNQNNY, followed by LYQLEN, MVGGVV-2, VQIVYK, SSTSAA, and GGVVIA. The statistics result indicates that hydrophobic residues play a key role in stabilizing the zipper interface. Single point and two linkage mutants of MVGGVV-1 confirmed that both Met1 and Val2 are key hydrophobic residues. This is consistent with the statistics analysis. The stability results of oligomer for MVGGVV-1 suggest that the intermediate state should be trimer (3-0) and tetramer (2-2). These methods can be used in stabilization study of other amyloid fibril.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Chen Y,He YJ,Wu M,Yan G,Li Y,Zhang J,Chen HF

doi

10.1002/bip.21405

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

578-86

issue

6

eissn

0006-3525

issn

1097-0282

journal_volume

93

pub_type

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