The role of alpha-synuclein (alpha S) amyloid fibrillation has been recognized in
various neurological diseases including Parkinson's Disease (PD). In early stages,
fibrillation occurs by the structural transition from helix to extended states in
monomeric alpha S followed by the formation of beta-sheets. This alpha-helix to beta-sheet
transition (alpha beta T) speeds up the formation of amyloid fibrils through the formation
of unstable and temporary configurations of the alpha S. In this study, the most important
regions that act as initiating nuclei and make unstable the initial configuration
were identified based on sequence and structural information. In this regard, a Targeted
Molecular Dynamics (TMD) simulation was employed using explicit solvent models under
physiological conditions. Identified regions are those that are in the early steps
of structural opening. The trajectory was clustered the structures characterized the
intermediate states. The findings of this study would help us to better understanding
of the mechanism of amyloid fibril formation.
