Weinkam, Patrick and Pletneva, Ekaterina V. and Gray, Harry B. and Winkler, Jay R. and Wolynes, Peter G. (2009) Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles. Proceedings of the National Academy of Sciences of the United States of America, 106 (6). pp. 1796-1801. ISSN 0027-8424 http://resolver.caltech.edu/CaltechAUTHORS:WEIpnas09
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The denatured state of proteins is heterogeneous and susceptible to general hydrophobic and electrostatic forces, but to what extent does the funneled nature of protein energy landscapes play a role in the unfolded ensemble? We simulate the denatured ensemble of cytochrome c using a series of models. The models pinpoint the efficacy of incorporating energetic funnels toward the native state in contrast with models having no native structure-seeking tendency. These models also contain varying strengths of electrostatic effects and hydrophobic collapse. The simulations based on these models are compared with experimental distributions for the distances between a fluorescent donor and the heme acceptor that were extracted from time-resolved fluorescence energy transfer experiments on cytochrome c. Comparing simulations to detailed experimental data on several labeling sites allows us to quantify the dominant forces in denatured protein ensembles.
|Additional Information:||© 2009 by The National Academy of Sciences of the USA. Contributed by Harry B. Gray, December 23, 2008 (sent for review December 3, 2008). Published online before print January 30, 2009, doi: 10.1073/pnas.0813120106 We thank Garyk Papoian for advice on making the funnel images. This work was supported by National Institutes of Health Grants GM044557 (to P.G.W.), GM068461 (to J.R.W.), and DK019038 (to H.B.G.) and by National Science Foundation Center for Theoretical Biological Physics Grant PHY-0822283. Author contributions: P.W. and P.G.W. designed research; P.W. performed research; P.W., E.V.P., H.B.G., J.R.W., and P.G.W. contributed new reagents/analytic tools; P.W., E.V.P., H.B.G., J.R.W., and P.G.W. analyzed data; and P.W., E.V.P., H.B.G., J.R.W., and P.G.W. wrote the paper. The authors declare no conflict of interest.|
|Subject Keywords:||denatured state; funnel; hydrophobic collapse; structure-based|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||06 Feb 2009 05:02|
|Last Modified:||26 Dec 2012 10:46|
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