Molecular dynamics simulations of amyloid-β(29–42) aggregation in bulk water and at the air–water interface

Abstract

Oligomers of amyloid-β (Aβ) peptides are related to Alzheimer’s disease, and their formation is accelerated at hydrophilic–hydrophobic interfaces. We performed all-atom molecular dynamics simulations of Aβ(29–42) peptides in bulk water and at an air–water interface. In bulk water, the fragments formed stable aggregates, and the secondary structures were hardly changed. At the interface, the peptides were more easily separated from each other due to the low free-energy barrier and changed their secondary structures more frequently. This conformational flexibility is likely to promote amyloid fibril growth, suggesting a key role of interfacial environments in early aggregation processes.

Caption of Graphical Abstract

Amyloid-β (Aβ) peptide aggregation is a key process in Alzheimer’s disease and is promoted at hydrophilic–hydrophobic interfaces. We performed all-atom molecular dynamics simulations of Aβ(29–42) peptides in bulk water and at an air–water interface. While stable aggregates formed in bulk water, the peptides at the interface showed enhanced dissociation and frequent structural changes due to a low free-energy barrier. This conformational flexibility likely promotes amyloid fibril formation, providing molecular-level insights into how interfacial environments such as membranes or lipid surfaces accelerate pathogenic aggregation.