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.
All Science Journal Classification (ASJC) codes
- Electronic, Optical and Magnetic Materials
- Atomic and Molecular Physics, and Optics
- Condensed Matter Physics
- Physical and Theoretical Chemistry
- Materials Chemistry