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Urea and guanidinium induced denaturation of a Trp-cage miniprotein

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Details

Original languageEnglish
Pages (from-to)8910-8924
Number of pages15
JournalJournal of Physical Chemistry Part B
Volume115
Issue number28
DOIs
Publication statusPublished - 21 Jul 2011
Publication typeA1 Journal article-refereed

Abstract

Using a combination of experimental techniques (circular dichroism, differential scanning calorimetry, and NMR) and molecular dynamics simulations, we performed an extensive study of denaturation of the Trp-cage miniprotein by urea and guanidinium. The experiments, despite their different sensitivities to various aspects of the denaturation process, consistently point to simple, two-state unfolding process. Microsecond molecular dynamics simulations with a femtosecond time resolution allow us to unravel the detailed molecular mechanism of Trp-cage unfolding. The process starts with a destabilizing proline shift in the hydrophobic core of the miniprotein, followed by a gradual destruction of the hydrophobic loop and the α-helix. Despite differences in interactions of urea vs guanidinium with various peptide moieties, the overall destabilizing action of these two denaturants on Trp-cage is very similar.