Molecular dynamics simulations on β amyloid peptide (25-35) in aqueous trifluoroethanol solution

Abstract

Amyloid peptide (Aβ) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. β-amyloid peptide (25-35) (Aβ25-35) is biologically active fragment of Aβ. The three-dimensional structure of Aβ25-35 in aqueous solution with 50% (vol/vol) TFE determined by NMR spectroscopy previously adopts an α-helical conformation from Ala30 to Met35. It has been proposed that Aβ(25-35) exhibits pH- and concentration-dependent α-helix ↔ β-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 α-helix formation of Aβ25-35 peptide by TFE, which particularly stabilizes α-helical conformation, we studied the secondary-structural elements of Aβ25-35 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 Aβ25-35 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 α-helical structure forming solvent.