Molecular Dynamics Simulations of the effect of Trifluoroethanol on the Conformation of asynuclein peptide

The accumulation of alpha-synuclein (α-syn) fibrils in neuronal inclusions is the defining pathologicalprocess in Parkinson disease (PD). Solvation structure and association alpha-synuclein (α-syn) in aqueousTFE solutions are investigated. Using molecular dynamics simulation and the AMBER03 force field. Thisconformational transition with concomitant peptide aggregation is a possible mechanism of plaqueformation. Here, in order to gain more insight into the mechanism of α-helix formation of α-syn peptide byTFE, which particularly stabilizes α- helical conformation, we studied the secondary-structural elements ofα-syn peptide by molecular dynamics simulations. Secondary structural elements determined from NMRspectroscopy in aqueous TFE solution are preserved during the MD simulation. TFE/water mixed solventhas reduced capacity for forming hydrogen bond to the peptide compared to pure water solvent. TFE allowsα-syn to form bifurcated hydrogen bonds to TFE as well as to residues in peptide itself. MD simulation inthis study supports the notion that TFE can act as a α-helical structure forming solvent.

Keywords:

Alpha-synuclein (α-syn) , Parkinson disease (PD) , Hydrogen bond , TFE , MD simulation