| Summary: | The destructive effect of Aβ peptides on membranes is an important source of its cytotoxicity in the pathogenesis of Alzheimer’s disease. We have investigated the binding mechanism between the Aβ42 peptide and bilayer in our former work. However, as another abundant form of Aβ peptides in the physiological environment, the binding mechanism between Aβ40 peptide and the lipid bilayer still remains ambiguous. Hence, we performed all-atom simulations on the Aβ40 peptides with the lipid bilayer herein using replica exchange with the solute tempering 2 method. We obtained four major binding models with the hydrophobic C-terminus as the most preferable binding region. Hydrophobic residues and positively charged residues are the principal residues involved in the peptide-bilayer interactions. Aβ40 peptides in our simulation mainly adopt a β-rich conformation in both bound and unbound states. Besides, we determined peptide-water interactions and found that bound peptides prefer forming hydrogen bonds with water molecules than unbound peptides. Our findings herein may provide new insights for the in-depth understanding of the membrane-destructive mechanism of Aβ peptides.
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