Trimethylamine- N -oxide's effect on polypeptide solvation at high pressure

A molecular dynamics simulation study

Rahul Sarma, Sandip Paul

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The solvation characteristics of a 15-residue polypeptide and also the structure of the solution in the presence and absence of trimethylamine-N-oxide (TMAO), one of the strongest known protein stabilizers among the natural osmolytes both at low and high pressures, are investigated under high pressure conditions by employing the molecular dynamics simulation technique. The goal is to provide a molecular level understanding of how TMAO protects proteins at elevated pressures. Two different conformations of the polypeptide are used: helix and extended. Analysis of peptide hydration characteristics reveals that the pressure-induced enhancement of hydration number is higher for the extended state as compared to the helix. TMAO shows an opposite effect and causes more dehydration of the extended state. The total number of atomic sites that solvate peptide residues increases in the presence of TMAO, whereas the number of hydrogen bonds formed by peptide with solution species reduces due to the inability of TMAO to donate its hydrogen to peptide hydrogen bonding sites. In solution, both hydrophobic and hydrogen bonding sites of TMAO are found to be well solvated by water molecules and solvation of TMAO enhances water structure and reduces the number of nearest identical neighbors for water. Pressure and TMAO are seen to have counteracting effects on water structural properties. Implications of these results for counteracting mechanism of TMAO are discussed.

Original languageEnglish (US)
Pages (from-to)9056-9066
Number of pages11
JournalJournal of Physical Chemistry B
Volume117
Issue number30
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Polypeptides
polypeptides
Solvation
solvation
Molecular dynamics
molecular dynamics
Peptides
Oxides
oxides
Computer simulation
peptides
simulation
Hydrogen bonds
Water
Hydration
helices
water
hydration
hydrogen
proteins

ASJC Scopus subject areas

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

Cite this

Trimethylamine- N -oxide's effect on polypeptide solvation at high pressure : A molecular dynamics simulation study. / Sarma, Rahul; Paul, Sandip.

In: Journal of Physical Chemistry B, Vol. 117, No. 30, 01.08.2013, p. 9056-9066.

Research output: Contribution to journalArticle

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