Fibrillated aggregation of amyloid β (Aβ) peptides is a potential factor causing toxic amyloid deposition in neurodegenerative diseases. A toxic fibril formation of Aβ is known to be enhanced on the ganglioside-rich lipid membrane containing some amounts of cholesterol and sphingomyelin. This ganglioside-rich membrane is supposed to provide a hydrophobic environment that promotes the formation of Aβ fibrils. Molecular dynamics simulations were carried out to investigate the structure of Aβ complex in the hydrophobic solution composed of dioxane and water molecules. The Aβ conformation was contrasted to that in the aqueous condition by executing multiple computational trials with the calculation models containing one, four, or six Aβ peptides. The conformation was also compared between the calculations with the 42-mer (Aβ42) and 40-mer (Aβ40) peptides. The simulations for Aβ42 demonstrated that Aβ peptides had a tendency to stretch out in the hydrophobic environment. In contrast, Aβ peptides were closely packed in the aqueous solution, and the motions of Aβ peptides were suppressed significantly. The N-terminal polar domains of Aβ peptides tended to be positioned at the inside of the Aβ complex in the hydrophobic environment, which supported the C-terminal domains in expanding outward for inter-molecular interaction. Since Aβ peptides were not tightly packed in the hydrophobic environment, the total surface area of the Aβ complex in the hydrophobic solution was larger than that in the aqueous one. The simulation for Aβ40 peptides also showed a difference between the hydrophobic and aqueous solutions. The difference was compatible with the results of Aβ42 in the structure of the Aβ complex, while the C-terminal outward expansion was not so distinct as Aβ42 peptides.
Keywords: amyloid β-peptide; complex conformation; hydrophobic environment; molecular dynamics simulation; peptide fibril.