Effects of Trimethylamine- N-oxide (TMAO) on Hydrophobic and Charged Interactions

Document Type

Article

Publication Date

5-31-2018

Abstract

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.

Identifier

85048202717 (Scopus)

Publication Title

Journal of Physical Chemistry B

External Full Text Location

https://doi.org/10.1021/acs.jpcb.7b11847

e-ISSN

15205207

ISSN

15206106

PubMed ID

29482320

First Page

5557

Last Page

5566

Issue

21

Volume

122

Grant

58024-ND6

Fund Ref

Nanjing Institute of Technology

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