TY - JOUR
T1 - Effects of Trimethylamine- N-oxide (TMAO) on Hydrophobic and Charged Interactions
AU - Su, Zhaoqian
AU - Ravindhran, Gopal
AU - Dias, Cristiano L.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/5/31
Y1 - 2018/5/31
N2 - Effects of trimethylamine-N-oxide (TMAO) on hydrophobic and charge-charge interactions are investigated using molecular dynamics simulations. Recently, these interactions in model peptides and in the Trp-Cage miniprotein have been reported to be strongly affected by TMAO. Neopentane dimers and Na+Cl- are used, here, as models for hydrophobic and charge-charge interactions, respectively. Distance-dependent interactions, i.e., potential of mean force, are computed using an umbrella sampling protocol at different temperatures which allows us to determine enthalpy and entropic energies. We find that the large favorable entropic energy and the unfavorable enthalpy, which are characteristic of hydrophobic interactions, become smaller when TMAO is added to water. These changes account for a negligible effect and a stabilizing effect on the strength of hydrophobic interactions for simulations performed with Kast and Netz models of TMAO, respectively. Effects of TMAO on the enthalpy are mainly due to changes in terms of the potential energy involving solvent-solvent molecules. At the molecular level, TMAO is incorporated in the solvation shell of neopentane which may explain its effect on the enthalpy and entropic energy. Charge-charge interactions become stronger when TMAO is added to water because this osmolyte decreases the enthalpic penalty of bringing Na+ and Cl- close together mainly by affecting ion-solvent interactions. TMAO is attracted to Na+, becoming part of its solvation shell, whereas it is excluded from the vicinity of Cl-. These results are more pronounced for simulation performed with the Netz model which is more hydrophobic and has a larger dipole moment compared to the Kast model of TMAO.
AB - Effects of trimethylamine-N-oxide (TMAO) on hydrophobic and charge-charge interactions are investigated using molecular dynamics simulations. Recently, these interactions in model peptides and in the Trp-Cage miniprotein have been reported to be strongly affected by TMAO. Neopentane dimers and Na+Cl- are used, here, as models for hydrophobic and charge-charge interactions, respectively. Distance-dependent interactions, i.e., potential of mean force, are computed using an umbrella sampling protocol at different temperatures which allows us to determine enthalpy and entropic energies. We find that the large favorable entropic energy and the unfavorable enthalpy, which are characteristic of hydrophobic interactions, become smaller when TMAO is added to water. These changes account for a negligible effect and a stabilizing effect on the strength of hydrophobic interactions for simulations performed with Kast and Netz models of TMAO, respectively. Effects of TMAO on the enthalpy are mainly due to changes in terms of the potential energy involving solvent-solvent molecules. At the molecular level, TMAO is incorporated in the solvation shell of neopentane which may explain its effect on the enthalpy and entropic energy. Charge-charge interactions become stronger when TMAO is added to water because this osmolyte decreases the enthalpic penalty of bringing Na+ and Cl- close together mainly by affecting ion-solvent interactions. TMAO is attracted to Na+, becoming part of its solvation shell, whereas it is excluded from the vicinity of Cl-. These results are more pronounced for simulation performed with the Netz model which is more hydrophobic and has a larger dipole moment compared to the Kast model of TMAO.
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U2 - 10.1021/acs.jpcb.7b11847
DO - 10.1021/acs.jpcb.7b11847
M3 - Article
C2 - 29482320
AN - SCOPUS:85048202717
SN - 1520-6106
VL - 122
SP - 5557
EP - 5566
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 21
ER -