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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.

SUBMITTER: Candotti M

PROVIDER: S-EPMC3625277 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Candotti Michela M Esteban-Martín Santiago S Salvatella Xavier X Orozco Modesto M

Proceedings of the National Academy of Sciences of the United States of America 20130327 15

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 prot ...[more]

PMID: 23536295

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