title: Salt Interactions in Solution Prevent Direct Association of Urea with a Peptide Backbone.
abstract: There is an ongoing debate as to how urea denatures proteins in solution. Using a combination of neutron scattering and computer simulation of a model peptide, KGPGK, it was found that the ionic strength and pH have a significant impact on the urea-peptide interaction. From the work presented here, it appears that urea first and foremost decreases the charge-based interactions in solution, such as the TFA-TFA association, before interacting with the peptide backbone via hydrogen bonds. This gives insight into the pH and salt concentration dependency of urea-caused protein denaturation and might unify direct and indirect theories of urea-induced protein denaturation. The observed differences between MD and neutron and X-ray diffraction data might show that MD, in this particular case, underestimates the influence of charged fluorinated solutes.
authors.affiliation: Department of Biochemistry, University of Oxford , Oxford OX1 3QU, U.K.
authors.forename: Nicola
authors.initials: N
authors.lastname: Steinke
authors.affiliation: Department of Physics, King's College London , London SE1 9NH, U.K.
authors.forename: Anna
authors.initials: A
authors.lastname: Genina
authors.affiliation: Department of Physics, King's College London , London SE1 9NH, U.K.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Lorenz
authors.affiliation: Department of Biochemistry, University of Oxford , Oxford OX1 3QU, U.K.
authors.forename: Sylvia E
authors.identifier: 0000-0002-3347-7759
authors.initials: SE
authors.lastname: McLain
mesh_terms: D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction; D009842:Oligopeptides / Q000737:chemistry*; D009994:Osmolar Concentration; D011489:Protein Denaturation; D012492:Salts / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D014269:Trifluoroacetic Acid / Q000737:chemistry*; D014508:Urea / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D009842:Oligopeptides; D012492:Salts; D012996:Solutions; D014508:Urea; D014269:Trifluoroacetic Acid