Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-beta Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation

Alzheimer's disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-beta (A beta) peptides. This review article presents molecular dynamics (MD) simulation studies of A beta peptides and A beta fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of A beta, a beta-hairpin structure promotes the formation of intermolecular beta-sheet structures. A beta peptides tend to exist at hydrophilic/hydrophobic interfaces and form more beta-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of A beta peptides, interact with A beta. An MD simulation study of the A beta amyloid fibrils in equilibrium is also presented: the A beta amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer's disease using MD simulations.