title: Toward an atomistic description of the urea-denatured state of proteins.
abstract: We present here the characterization of the structural, dynamics, and energetics of properties of the urea-denatured state of ubiquitin, a small prototypical soluble protein. By combining state-of-the-art molecular dynamics simulations with NMR and small-angle X-ray scattering data, we were able to: (i) define the unfolded state ensemble, (ii) understand the energetics stabilizing unfolded structures in urea, (iii) describe the dedifferential nature of the interactions of the fully unfolded proteins with urea and water, and (iv) characterize the early stages of protein refolding when chemically denatured proteins are transferred to native conditions. The results presented herein are unique in providing a complete picture of the chemically unfolded state of proteins and contribute to deciphering the mechanisms that stabilize the native state of proteins, as well as those that maintain them unfolded in the presence of urea.
authors.affiliation: Molecular Modelling and Bioinformatics Unit, Institute for Research in Biomedicine Barcelona, 08028 Barcelona, Spain.
authors.forename: Michela
authors.initials: M
authors.lastname: Candotti
authors.forename: Santiago
authors.initials: S
authors.lastname: Esteban-Martín
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D012997:Solvents / Q000737:chemistry; D013997:Time Factors; D025801:Ubiquitin / Q000737:chemistry*; D014508:Urea / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014965:X-Rays
chemical_list: D012997:Solvents; D025801:Ubiquitin; D014867:Water; D014508:Urea
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