Toward an atomistic description of the urea-denatured state of proteins.

TitleToward an atomistic description of the urea-denatured state of proteins.
Publication TypeJournal Article
Year of Publication2013
AuthorsCandotti, Michela, Esteban-Martín Santiago, Salvatella Xavier, and Orozco Modesto
JournalProc Natl Acad Sci U S A
Date Published2013 Apr 9
KeywordsComputer Simulation, Hydrogen Bonding, Hydrogen-Ion Concentration, Magnetic Resonance Spectroscopy, Molecular Dynamics Simulation, Protein Denaturation, Protein Folding, Protein Structure, Radiation, Scattering, Secondary, Solvents, Time Factors, Ubiquitin, Urea, Water, X-Rays

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.