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Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles

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. PMCID PMC2644117. https://resolver.caltech.edu/CaltechAUTHORS:WEIpnas09

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0813120106DOIArticle
http://www.pnas.org/cgi/doi/10.1073/pnas.0813120106PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644117/PubMed CentralArticle
ORCID:
AuthorORCID
Gray, Harry B.0000-0002-7937-7876
Winkler, Jay R.0000-0002-4453-9716
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.
Funders:
Funding AgencyGrant Number
NIHGM044557
NIHGM068461
NIHDK019038
NSFPHY-0822283
Subject Keywords:denatured state; funnel; hydrophobic collapse; structure-based
Issue or Number:6
PubMed Central ID:PMC2644117
Record Number:CaltechAUTHORS:WEIpnas09
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:WEIpnas09
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13254
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Feb 2009 05:02
Last Modified:22 Nov 2019 09:58

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