Urea and Guanidinium Induced Denaturation of a Trp-Cage Miniprotein

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• 作者：Jan Heyda ; Milan Koz虒i&#769 ; š ; ek ; Lucie Bedna虂rova ; Gary Thompson ; Jan Konvalinka ; Jir虒i&#769 ; Vondra虂š ; ek ; Pavel Jungwirth
• 刊名：Journal of Physical Chemistry B
• 出版年：2011
• 出版时间：July 21, 2011
• 年：2011
• 卷：115
• 期：28
• 页码：8910-8924
• 全文大小：1936K
• 年卷期：v.115,no.28(July 21, 2011)
• ISSN：1520-5207

文摘

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 伪-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.