Study of early stages of amyloid Aβ13-23 formation using molecular dynamics simulation in implicit environments

• Early stages of amyloid Aβ13-23 formation were studied using MD simulation.
• Initial α-helical conformations of peptides were changing into coil and β-sheets.
• A knowledge about Aβ13-23 aggregation might be useful for design of novel drugs.

β-amyloid aggregation and formation of senile plaques is one of the hallmarks of Alzheimer’s disease (AD). It leads to degeneration of neurons and decline of cognitive functions. The most aggregative and toxic form of β-amyloid is Aβ1-42 but in experiments, the shorter forms able to form aggregates are also used. The early stages of amyloid formation are of special interest due to the influence of this peptide on progression of AD. Here, we employed nine helices of undecapeptide Aβ13-23 and studied progress of amyloid formation using 500 ns molecular dynamics simulation and implicit membrane environment. The small β-sheets emerged very early during simulation as separated two-strand structures and a presence of the membrane facilitated this process. Later, the larger β-sheets were formed. However, the ninth helix which did not form paired structure stayed unchanged till the end of MD simulation. Paired helix–helix interactions seemed to be a driving force of β-sheet formation at early stages of amyloid formation. Contrary, the specific interactions between α-helix and β-sheet can be very stable and be stabilized by the membrane.

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