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Mechanism of α-Synuclein Translocation through a VDAC Nanopore Revealed by Energy Landscape Modeling of Escape Time Distributions

Published

Author(s)

David Paul Hoogerheide, Philip A. Gurnev, Tatiana K. Rostovtseva, Sergey M. Bezrukov

Abstract

We probe the energy landscape governing the passage of α-synuclein, a natural "diblock copolymer"-like polypeptide, through a nanoscale pore. The motion of this electrically heterogeneous disordered polymer in the voltage-dependent anion channel (VDAC) strongly depends on the properties of both the charged and uncharged regions of the polymer. This allows the energy landscape to be modeled using a drift-diffusion framework that incorporates the α-synuclein binding energy and the free energy cost of its confinement in the VDAC pore, with ramifications for the physiological role of α-synuclein.
Citation
Nanoscale
Volume
9

Keywords

alpha synuclein, Parkinson disease, voltage dependent anion channel, nanopore, free energy landscape, Markov Chain Monte Carlo optimization, polymer transport and translocation, Markov processes, first passage

Citation

, D. , , P. , , T. and , S. (2016), Mechanism of α-Synuclein Translocation through a VDAC Nanopore Revealed by Energy Landscape Modeling of Escape Time Distributions, Nanoscale, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=921707 (Accessed July 13, 2024)

Issues

If you have any questions about this publication or are having problems accessing it, please contact reflib@nist.gov.

Created November 17, 2016, Updated February 19, 2017