Survey of the Aβ-peptide structural diversity: molecular dynamics approaches.

Unlabelled: The review deals with the application of Molecular Dynamics (MD) to the structure modeling of beta-amyloids (Aβ), currently classified as intrinsically disordered proteins (IDPs). In this review, we strive to relate the main advances in this area but specifically focus on the approaches and methodology. All relevant papers on the Aβ modeling are cited in the Tables in Supplementary Data, including a concise description of the applied approaches, sorted according to the types of the studied systems: modeling of the monomeric Aβ and Aβ aggregates.

Structure Comparison of Beta Amyloid Peptide Aβ 1-42 Isoforms. Molecular Dynamics Modeling.

Beta amyloid peptide Aβ 1-42 (Aβ42) has a unique dual role in the human organism, as both the peptide with an important physiological function and one of the most toxic biological compounds provoking Alzheimer's disease (AD). There are several known Aβ42 isoforms that we discuss here that are highly neurotoxic and lead to the early onset of AD. Aβ42 is an intrinsically disordered protein with no experimentally solved structure under physiological conditions.

Molecular Mechanism of Zinc-Dependent Oligomerization of Alzheimer's Amyloid-β with Taiwan (D7H) Mutation.

Amyloid-β (Aβ) is a peptide formed by 39-43 amino acids, heterogenous by the length of its C-terminus. Aβ constitutes a subnanomolar monomeric component of human biological fluids; however, in sporadic variants of Alzheimer's disease (AD), it forms soluble neurotoxic oligomers and accumulates as insoluble extracellular polymeric aggregates (amyloid plaques) in the brain tissues. The plaque formation is controlled by zinc ions; therefore, abnormal interactions between the ions and Aβ seem to take part in the triggering of sporadic AD.

Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.

The pathogenesis of Alzheimer's disease (AD) is associated with the formation of cerebral amyloid plaques, the main components of which are the modified Aβ molecules as well as the metal ions. Aβ isomerized at Asp7 residue (isoD7-Aβ) is the most abundant isoform in amyloid plaques. We hypothesized that the pathogenic effect of isoD7-Aβ is due to the formation of zinc-dependent oligomers, and that this interaction can be disrupted by the rationally designed tetrapeptide (HAEE).