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Determination of the Free Energy Landscape of a-Synuclein Using Spin Label Nuclear Magnetic Resonance Measurements

journal contribution
posted on 2023-06-07, 20:21 authored by Jane R Allison, Peter Varnai, Christopher M Dobson, Michele Vendruscolo
Natively unfolded proteins present a challenge for structure determination because they populate highly heterogeneous ensembles of conformations. A useful source of structural information about these states is provided by paramagnetic relaxation enhancement measurements by nuclear magnetic resonance spectroscopy, from which long-range interatomic distances can be estimated. Here we describe a method for using such distances as restraints in molecular dynamics simulations to obtain a mapping of the free energy landscapes of natively unfolded proteins. We demonstrate the method in the case of a-synuclein and validate the results by a comparison with electron transfer measurements. Our findings indicate that our procedure provides an accurate estimate of the relative statistical weights of the different conformations populated by a-synuclein in its natively unfolded state.

History

Publication status

  • Published

Journal

Journal of the American Chemical Society

ISSN

0002-7863

Publisher

American Chemical Society

Issue

51

Volume

131

Page range

18314-18326

Pages

13.0

Department affiliated with

  • Chemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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