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

Allison, Jane R, Varnai, Peter, Dobson, Christopher M and Vendruscolo, Michele (2009) Determination of the Free Energy Landscape of a-Synuclein Using Spin Label Nuclear Magnetic Resonance Measurements. Journal of the American Chemical Society, 131 (51). pp. 18314-18326. ISSN 0002-7863

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Depositing User: Peter Varnai
Date Deposited: 06 Feb 2012 18:31
Last Modified: 02 May 2012 14:08
URI: http://sro.sussex.ac.uk/id/eprint/16886
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