Molecular insight into different denaturing efficiency of urea, guanidinium, and methanol: A comparative simulation study

Takahiro Koishi, Kenji Yasuoka, Soohaeng Yoo Willow, Shigenori Fujikawa, Xiao Cheng Zeng

Research output: Contribution to journalArticle

18 Scopus citations


We have designed various nanoslit systems, whose opposing surfaces can be either hydrophobic, hydrophilic, or simply a water-vapor interface, for the molecular dynamics simulation of confined water with three different protein denaturants, i.e., urea, guanidinium chloride (GdmCl), and methanol, respectively. Particular attention is placed on the preferential adsorption of the denaturant molecules onto the opposing surfaces and associated resident time in the vicinal layer next to the surfaces, as well as their implication in the denaturing efficiency of different denaturant molecules. Our simulation results show that among the three denaturants, the occupancy of methanol in the vicinal layer is the highest while the residence time of Gdm is the longest. Although the occupancy and the residence time of urea in the vicinal layer is less than those of the other two denaturant molecules, urea entails "all-around" properties for being a highly effective denaturant. The distinct characteristics of three denaturants may suggest a different molecular mechanism for the protein denaturation. This comparative simulation by design allows us to gain additional insights, on the molecular level, into the denaturation effect and related hydrophobic effect.

Original languageEnglish (US)
Pages (from-to)2540-2551
Number of pages12
JournalJournal of Chemical Theory and Computation
Issue number6
Publication statusPublished - Jun 11 2013


ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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