, 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 March 14, 2025)
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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)
, 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
Pub Type
Journals
Download Paper
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
Issues
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Created November 17, 2016, Updated February 19, 2017