Discrete molecular dynamics study of Alzheimer amyloid ��-protein (A��) folding (original) (raw)

Aβ folding and assembly are believed to be seminal pathogenic events in Alzheimer's disease. We study Aβ(1-42) folding by discrete molecular dynamics using a four-bead protein model with hydrogen bonds and amino acid-specific interactions. Interactions account for hydrophobic/hydrophilic effect that mimic the solvent as well as electrostatic effects. We study monomer conformations on a wide temperature range. At each temperature, we find many different monomer conformations, indicating that Aβ(1-42) folding is not unique. At low temperatures, we observe globular conformations with some α-helical content while at higher temperatures β-strand-rich conformations with no α-helical content are present. This temperature-driven conformational change is consistent with experimental findings by Gursky and Aleshkov. Varying the strength of electrostatics interactions, we show that all monomer conformations become more compact. β-strand-rich conformations are characterized by turn regions centered at D23-K28 and G37-G38, and β-strands at L17-A21, I31-V36 and V39-A42, which are important in fibril formation.

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