TY - JOUR
T1 - Individual and combined effects of urea and trimethylamine N-oxide (TMAO) on protein structures
AU - Su, Zhaoqian
AU - Dias, Cristiano L.
N1 - Funding Information:
Computational resources for this work were provided by the High Performance Computer Center at the New Jersey Institute of Technology and Compute Canada.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molliq.2019.111443
DO - 10.1016/j.molliq.2019.111443
M3 - Article
AN - SCOPUS:85070259489
SN - 0167-7322
VL - 293
JO - Journal of Molecular Liquids
JF - Journal of Molecular Liquids
M1 - 111443
ER -