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

Amyloid beta-peptide (A beta) is the major component of plaques found in the brains of Alzheimer's patients. Among its two predominate forms A beta(1-40) and A beta(1-42), the latter possesses stronger aggregation and deposition propensity than the former. To explore the conformational preference of A beta(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-trifluoro-ethanol (TFE), water, and dimethyl sulfoxide (DMSO). Structural analyses demonstrate that there are two stable helix regions of A beta(1-42) in HFIP and TFE, supporting the idea that they act as helix-promoting solvents. In aqueous Solution, alpha-helix to p-sheet conformational transition is observed in the C-terminal domain of A beta(1-42). However, in pure DMSO, the unfolding of C-terminal region occurs, but no beta-sheet structure is observed. The primary mechanism of conformational behaviors of A beta(1-42) in the four solvents mentioned above is analyzed and discussed based on the results of MD simulations. (c) 2008 Elsevier B.V. All rights reserved.