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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 VendruscoloNatively 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.
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Publication status
- Published
Journal
Journal of the American Chemical SocietyISSN
0002-7863Publisher
American Chemical SocietyExternal DOI
Issue
51Volume
131Page range
18314-18326Pages
13.0Department affiliated with
- Chemistry Publications
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- No
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- Yes
Legacy Posted Date
2012-02-06Usage metrics
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