title: Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles.
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.
authors.affiliation: Center for Theoretical Biological Physics and Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weinkam
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Pletneva
authors.forename: Harry B
authors.initials: HB
authors.lastname: Gray
authors.forename: Jay R
authors.initials: JR
authors.lastname: Winkler
authors.forename: Peter G
authors.initials: PG
authors.lastname: Wolynes
mesh_terms: D003198:Computer Simulation; D045304:Cytochromes c / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D055672:Static Electricity
chemical_list: D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D045304:Cytochromes c