Charge states rather than propensity for β‐structure determine enhanced fibrillogenesis in wild‐type Alzheimer's β‐amyloid peptide compared to E22Q Dutch mutant

摘要: The activity of the Alzheimer's amyloid β-peptide is a sensitive function peptide's sequence. Increased fibril elongation rate E22Q Dutch mutant relative to that wild-type peptide has been observed. increased attributed larger propensity for formation β structure in monomeric solution WT peptide. That hypothesis tested using four nanosecond timescale simulations and forms Aβ(10–35)-peptide aqueous solution. simulation results indicate β-structure no greater than A significant measure "flickering" helical central hydrophobic cluster region both peptides argue against mutation leads higher probability We propose stability solvated decreased former. Stability difference due differing charge state two peptides. other proposal prediction rates should be similar under acid conditions.