The effect of aqueous solutions of trimethylamine-N-oxide on pressure induced modifications of hydrophobic interactions

Rahul Sarma, Sandip Paul

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

To understand the mechanism of protein protection by the osmolyte trimethylamine-N-oxide (TMAO) at high pressure, using molecular dynamics (MD) simulations, solvation of hydrophobic group is probed in aqueous solutions of TMAO over a wide range of pressures relevant to protein denaturation. The hydrophobic solute considered in this study is neopentane which is a considerably large molecule. The concentrations of TMAO range from 0 to 4 M and for each TMAO concentration, simulations are performed at five different pressures ranging from 1 atm to 8000 atm. Potentials of mean force are calculated and the relative stability of solvent-separated state over the associated state of hydrophobic solute are estimated. Results suggest that high pressure reduces association of hydrophobic solutes. From computations of site-site radial distribution function followed by analysis of coordination number, it is found that water molecules are tightly packed around the nonpolar particle at high pressure and the hydration number increases with increasing pressure. On the other hand, neopentane interacts preferentially with TMAO over water and although hydration of neopentane reduces in presence of this osmolyte, TMAO does not show any tendency to prevent the pressure-induced dispersion of neopentane moieties. It is also observed that TMAO molecules prefer a side-on orientation near the neopentane surface, allowing its oxygen atom to form favorable hydrogen bonds with water while maintaining some hydrophobic contacts with neopentane. Analysis of hydrogen-bond properties and solvation characteristics of TMAO reveals that TMAO can form hydrogen bonds with water and it reduces the identical nearest neighbor water molecules caused by high hydrostatic pressures. Moreover, TMAO enhances life-time of water-water hydrogen bonds and makes these hydrogen bonds more attractive. Implication of these results for counteracting effect of TMAO against protein denaturation at high pressures are discussed.

Original languageEnglish (US)
Article number094502
JournalJournal of Chemical Physics
Volume137
Issue number9
DOIs
StatePublished - Sep 7 2012
Externally publishedYes

Fingerprint

Hydrophobic and Hydrophilic Interactions
neopentane
aqueous solutions
Pressure
oxides
Hydrogen
Hydrogen bonds
Water
interactions
hydrogen bonds
water
Protein Denaturation
solutes
Denaturation
Molecules
biopolymer denaturation
Solvation
Hydration
solvation
hydration

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry
  • Medicine(all)

Cite this

The effect of aqueous solutions of trimethylamine-N-oxide on pressure induced modifications of hydrophobic interactions. / Sarma, Rahul; Paul, Sandip.

In: Journal of Chemical Physics, Vol. 137, No. 9, 094502, 07.09.2012.

Research output: Contribution to journalArticle

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