Molecular Dynamics Simulations on β Amyloid Peptide (25-35) in Aqueous Trifluoroethanol Solution

Amyloid peptide (A${\beta}$) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. ${\beta}$-amyloid peptide (25-35) (A${\beta}$25-35) is biologically active fragment of A${\beta}$. The three-dimensional structure of A${\beta}$25-35 in aqueous solution with 50% (vol/vol) TFE determined by NMR spectroscopy previously adopts an ${\alpha}$-helical conformation from $Ala^{30}$ to $Met^{35}$. It has been proposed that A${\beta}$(25-35) exhibits pH- and concentration-dependent ${\alpha}-helix{\leftrightarrow}{\beta}$sheet transition. This conformational transition with concomitant peptide aggregation is a possible mechanism of plaque formation. Here, in order to gain more insight into the mechanism of ${\alpha}$-helix formation of A${\beta}$25-35 peptide by TFE, which particularly stabilizes ${\alpha}$-helical conformation, we studied the secondary-structural elements of A${\beta}$25-35 peptide by molecular dynamics simulations. Secondary structural elements determined from NMR spectroscopy in aqueous TFE solution are preserved during the MD simulation. TFE/water mixed solvent has reduced capacity for forming hydrogen bond to the peptide compared to pure water solvent. TFE allows A${\beta}$25-35 to form bifurcated hydrogen bonds to TFE as well as to residues in peptide itself. MD simulation in this study supports the notion that TFE can act as an ${\alpha}$-helical structure forming solvent.