Conformational ensemble of human alpha-synuclein physiological form predicted by molecular simulations

We perform here enhanced sampling simulations of N-terminally acetylated human ?-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post-translational modification leads to the formation of a transient amphipathic ?-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.