Molecular Dynamics Simulation of the Conformational Transition of Amyloid Peptide 42 Inhibited by Trehalose

The molecular mechanism of the conformational transition of amyloid peptide 42(A beta 42) inhibited by trehalose was studied using molecular dynamics simulation. It is confirmed that the conformational transition of A beta 42 is prevented by trehalose in a dose. dependent manner. In water and low. concentration trehalose (0.18 mol.L-1) solutions, A beta 42 transforms from its initial alpha-helix to a beta-sheet. In 0.37 mol.L-1 trehalose, however, the conformational transition of A beta 42 is prevented. It is obvious that there is a hydration shell within about 0.2 nm from the closest atoms of A beta 42 on the peptide surface, which is caused by the preferential exclusion of trehalose. Trehalose molecules cluster around the peptide at a distance of 0.4 nm. In addition, the intra. peptide hydrophobic interactions are weakened and the number of long range contacts of A beta 42 is decreased by trehalose. Therefore, the hydrophobic collapse of the peptide is alleviated and the conformational transition is inhibited. These findings are important for the rational design of a highly efficient inhibitor for Alzheimer's disease.