Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles |
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| Authors: | Patrick Weinkam Ekaterina V. Pletneva Harry B. Gray Jay R. Winkler Peter G. Wolynes |
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| Affiliation: | aCenter for Theoretical Biological Physics and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; and ;bBeckman Institute, California Institute of Technology, Pasadena, CA 91125 |
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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. |
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| Keywords: | denatured state funnel hydrophobic collapse structure-based |
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