Effects of Zn2+ binding on the structural and dynamic properties of amyloid β peptide associated with Alzheimer's disease: Asp1 or Glu11?

ABSTRACT: Extensive experimental and computational studies have suggested that multiple Zn(2+) binding modes in amyloid β (Aβ) peptides could exist simultaneously. However, consistent results have not been obtained for the effects of Zn(2+) binding on Aβ structure, dynamics, and kinetics in particular. Some key questions such as why it is so difficult to distinguish the polymorphic states of metal ions binding to Aβ and what the underlying rationale is, necessitate elucidation. In this work, two 3N1O Zn(2+) binding modes were constructed with three histidines (His(6), His(13), and His(14)), and Asp(1)/Glu(11) of Aβ40 coordinated to Zn(2+). Results from molecular dynamics simulations reveal that the conformational ensembles of different Zn(2+)-Aβ40 complexes are nonoverlapping. The formation of turn

SUBMITTER: Xu L 

PROVIDER: S-EPMC3837377 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature