title: Phase transitions and structure analysis in wild-type, A30P, E46K, and A53T mutants of α-synuclein.
abstract: α-Synuclein has been implicated in the development of neural plaques in Parkinson's Disease and Lewy-Body Dementia. This paper reports on the structural phase change behavior exhibited over a relevant range of temperatures in canonical protein Monte Carlo simulations for wild-type α-synuclein and three of its familial variants. We performed and analyzed these simulations to determine residue occupancy variations above and below this phase transition. From this analysis, we found regions above the phase transition temperature that consistently exhibited increased propensity for formation of long-chain beta-sheets, suggesting a possible role in α-synuclein aggregation.
authors.affiliation: Department of Physics, University of Alberta, Edmonton, AB, T6G2E1, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Healey
authors.affiliation: Department of Physics, University of Alberta, Edmonton, AB, T6G2E1, Canada.|National Institute for Nanotechnology, National Research Council, Edmonton, AB, T6G2M9, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Woodside
authors.affiliation: Department of Physics, University of Alberta, Edmonton, AB, T6G2E1, Canada. jtus@phys.ualberta.ca.|Department of Oncology, University of Alberta, Edmonton, AB, T6G1Z2, Canada. jtus@phys.ualberta.ca.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
mesh_terms: D009010:Monte Carlo Method; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics*; D009154:Mutation; D044367:Phase Transition; D017433:Protein Structure, Secondary; D044366:Transition Temperature; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D051844:alpha-Synuclein
keywords: Intrinsically disordered protein; Monte Carlo simulations; Mutations; Parkinson’s disease; Phase transitions; α-Synuclein