title: Conformational ensemble of human α-synuclein physiological form predicted by molecular simulations.
abstract: We perform here enhanced sampling simulations of N-terminally acetylated human α-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 α-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany. p.carloni@fz-juelich.de and Jülich Supercomputing Centre, Forschungszentrum Jülich, 52425 Jülich, Germany and Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University, Aachen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany. p.carloni@fz-juelich.de and Scuola Internazionale Superiore di Studi Avanzati (SISSA/ISAS), via Bonomea 265, 34136 Trieste, Italy and Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology, University of Bologna, 40127 Bologna, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Musiani
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany. p.carloni@fz-juelich.de and German Research School for Simulation Sciences, Forschungszentrum Jülich, 52425 Jülich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Abad
authors.affiliation: German Research School for Simulation Sciences, Forschungszentrum Jülich, 52425 Jülich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dibenedetto
authors.affiliation: Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, 52056 Aachen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Mouhib
authors.affiliation: Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR), Universidad Nacional de Rosario, 27 de Febrero 210 bis, S2002LRK-Rosario, Argentina and Institute for Drug Discovery of Rosario (IIDEFAR), Universidad Nacional de Rosario, Rosario, 27 de Febrero 210 bis, S2002LRK-Rosario, Argentina.
authors.forename: C O
authors.initials: CO
authors.lastname: Fernandez
authors.affiliation: Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany. p.carloni@fz-juelich.de and German Research School for Simulation Sciences, Forschungszentrum Jülich, 52425 Jülich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Carloni
mesh_terms: D000107:Acetylation; D002942:Circular Dichroism; D006801:Humans; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010300:Parkinson Disease / Q000503:physiopathology; D011499:Protein Processing, Post-Translational; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein