The effect of solvents on the conformations of Amyloid β-peptide (1-42) studied by molecular dynamics simulation

Amyloid β-peptide (Aβ) is the major component of plaques found in the brains of Alzheimer's patients. Among its two predominate forms − Aβ(1-40) and Aβ(1-42), the latter possesses stronger aggregation and deposition propensity than the former. To explore the conformational preference of Aβ(1-42) in different solvents, molecular dynamics (MD) simulations are performed to investigate its secondary structures in the following four solvents: hexafluoroisopropanol (HFIP), 2,2,2-trifluoroethanol (TFE), water, and dimethyl sulfoxide (DMSO). Structural analyses demonstrate that there are two stable helix regions of Aβ(1-42) in HFIP and TFE, supporting the idea that they act as helix-promoting solvents. In aqueous solution, α-helix to β-sheet conformational transition is observed in the C-terminal domain of Aβ(1-42). However, in pure DMSO, the unfolding of C-terminal region occurs, but no β-sheet structure is observed. The primary mechanism of conformational behaviors of Aβ(1-42) in the four solvents mentioned above is analyzed and discussed based on the results of MD simulations.