Individual and combined effects of urea and trimethylamine N-oxide (TMAO) on protein structures

Zhaoqian Su, Cristiano L. Dias

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


In this manuscript, we perform all-atom molecular dynamics simulations of model peptides to study the molecular mechanisms accounting for individual and combined effects of two osmolytes, i.e., urea and trimethylamine N-oxide (TMAO). We find that urea, which is a denaturant osmolyte, destabilizes mainly hydrophobic and intra-backbone interactions. TMAO, which is a protecting osmolyte, stabilizes charge-charge and intra-backbone interactions whereas it destabilizes hydrophobic interactions. We show that charge-charge interactions are highly sensitive to the presence of TMAO and it may be the main interaction accounting for TMAO stabilizing effect on proteins. These charge-charge interactions are also shown to play a dominant role in how TMAO counteracts the effect of urea. These results are rationalized in terms of the preferential interaction of osmolytes.

Original languageEnglish (US)
Article number111443
JournalJournal of Molecular Liquids
StatePublished - Nov 1 2019

All Science Journal Classification (ASJC) codes

  • Electronic, Optical and Magnetic Materials
  • Atomic and Molecular Physics, and Optics
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Materials Chemistry


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