Exploring the molecular mechanism of trimethylamine-N-oxide's ability to counteract the protein denaturing effects of urea

Rahul Sarma, Sandip Paul

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Protein denaturation in highly concentrated urea solution is a well-known phenomenon. The counteracting effect of a naturally occurring osmolyte, trimethylamine-N-oxide (TMAO), against urea-conferred protein denaturation is also well-established. However, what is largely unknown is the mechanism by which TMAO counteracts this denaturation. To provide a molecular level understanding of how TMAO protects proteins in highly concentrated urea solution, we report here the structural, energetic, and dynamical properties of N-methylacetamide (NMA) solutions that also contain urea and/or TMAO. The solute NMA is of interest mainly because it contains the peptide linkage in addition to hydrophobic sites and represents the typical solvent-exposed state of proteins. Molecular dynamics computer simulation technique is employed in this study. Analysis of solvation characteristics reveals dehydration of NMA and reduction in hydrogen bond number between NMA oxygen and water upon addition of TMAO. The effect of TMAO on NMA-urea interaction is found to be insignificant. Because TMAO cannot donate its hydrogen to NMA oxygen, the total number of hydrogen bonds formed by NMA oxygen with solution species decreases in the presence of TMAO. In solution, TMAO is found to interact strongly with water and urea. Solvation of TMAO makes the water hydrogen bonding network relatively stronger and reduces relaxation of urea-water hydrogen bonds. Implications of these results for counteracting mechanism of TMAO are discussed.

Original languageEnglish (US)
Pages (from-to)5691-5704
Number of pages14
JournalJournal of Physical Chemistry B
Volume117
Issue number18
DOIs
StatePublished - May 9 2013
Externally publishedYes

Fingerprint

ureas
Urea
proteins
Proteins
Oxides
oxides
Denaturation
biopolymer denaturation
Hydrogen bonds
Water
Solvation
hydrogen bonds
Oxygen
water
solvation
oxygen
trimethyloxamine
Bond number
hydrogen
N-methylacetamide

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Exploring the molecular mechanism of trimethylamine-N-oxide's ability to counteract the protein denaturing effects of urea. / Sarma, Rahul; Paul, Sandip.

In: Journal of Physical Chemistry B, Vol. 117, No. 18, 09.05.2013, p. 5691-5704.

Research output: Contribution to journalArticle

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