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

摘要

Amyloid peptide (Abeta) is the major component of senile plaques found in the brain of patient of Alzheimer's disease.beta-amyloid peptide (25-35) (Abeta25-35) is biologically active fragment of Abeta.The three-dimensional structure of Abeta25-35 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 Abeta(25-35) exhibits pH- and concentration-dependent alpha-helix<-> 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 Abeta25-35 peptide by TFE,which particularly stabilizes alpha-helical conformation,we studied the secondary-structural elements of Abeta25-35 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 Abeta25-35 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.