title: Synchronous vs asynchronous chain motion in alpha-synuclein contact dynamics.
abstract: alpha-Synuclein (alpha-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson's disease. Tertiary contact formation rate constants in alpha-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in alpha-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide.
authors.affiliation: Department of Chemistry, DePaul University, 243 South Wabash Ave, Chicago, Illinois 60604-2301, USA.
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Urie
authors.forename: David
authors.initials: D
authors.lastname: Angulo
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lee
authors.forename: John J
authors.initials: JJ
authors.lastname: Kozak
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: Jay R
authors.initials: JR
authors.lastname: Winkler
mesh_terms: D003198:Computer Simulation; D008823:Micelles; D008958:Models, Molecular; D009010:Monte Carlo Method; D009038:Motion; D017434:Protein Structure, Tertiary; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D008823:Micelles; D051844:alpha-Synuclein