Raman Spectroscopic Signatures of Noncovalent Interactions Between Trimethylamine N-oxide (TMAO) and Water

Munroe, Katherine L.; Magers, David H.; Hammer, Nathan I.

doi:10.1021/jp203840w

Cited by 58 publications

(122 citation statements)

References 75 publications

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“…We also observed that the influence of Lysozyme on the structure of TMAO is more profound at lower osmolyte concentration, and decreases rapidly for higher protein concentrations, supporting the hypothesis that TMAO is preferentially excluded from the protein surface and that it prefers to strongly bind 2-3 water molecules in solutions. 63,66,68 In the case of Proline, spectral results indicate that Pro, although being a good protein stabilizer, interacts directly with the protein surface, and that the carboxyl group of Proline molecule plays a dominant role in these interactions ( Figure 8B). MD simulations confirm preferential binding of Proline to the Lysozyme surface.…”

Section: Discussionmentioning

confidence: 99%

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Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies

Bruździak

Adamczak

Kaczkowska

et al. 2015

Phys. Chem. Chem. Phys.

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Interactions between osmolytes and hen egg white lysozyme in aqueous solutions were studied by means of FTIR spectroscopy and molecular dynamics. A combination of difference spectra method and chemometric analysis of spectroscopic data was used to determine the number of osmolyte molecules interacting with the protein, and the preferential interaction coefficient in presented systems. Both osmolytes -l-proline and trimethylamine-N-oxide (TMAO) - belong to a group of stabilizing osmolytes, and according to the preferential exclusion/hydration hypothesis, both should be excluded from the vicinity of the protein backbone and surface. We provide experimental and computational evidence that although TMAO behaves according to the hypothesis, proline does not. Our results suggest that preferential exclusion is not a universal property of stabilizing osmolytes.

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Section: Discussionmentioning

confidence: 99%

“…TMAO is one of the best described stabilizing osmolytes, and many aspects of its hydration and interactions with proteins are known. According to Munroe et al 63 the band with a maximum at ca. 950 cm -1 can be attributed to N-O stretching vibration ( Figure 3).…”

Section: Lysozyme-affected Tmao Spectramentioning

confidence: 98%

Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies

Bruździak

Adamczak

Kaczkowska

et al. 2015

Phys. Chem. Chem. Phys.

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“…38 A strong hydration of TMAO was also seen in molecular dynamics simulations. 40 Raman spectroscopy indicates that TMAO has at least three H-bonds from neighboring water, 41 but the mere existence of H-bonded waters does not necessarily imply that all (or even any) of them are mandatory hydration waters. The spectroscopic observation that the solvation shell of TMAO contains slower moving water molecules 42 may be at least in part due to the solvation sites at the TMAO oxygen.…”

Section: Discussionmentioning

confidence: 99%

Volume Exclusion and H-Bonding Dominate the Thermodynamics and Solvation of Trimethylamine-N-oxide in Aqueous Urea

Rösgen

Jackson-Atogi

2012

J. Am. Chem. Soc.

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Trimethylamine-N-oxide (TMAO) and urea represent the extremes among the naturally occurring organic osmolytes in terms of their ability to stabilize/destabilize proteins. Their mixtures are found in nature and have generated interest in terms of both their physiological role and their potential use as additives in various applications (crystallography, drug formulation, etc.). Here we report experimental density and activity coefficient data for aqueous mixtures of TMAO with urea. From these data we derive the thermodynamics and solvation properties of the osmolytes, using Kirkwood–Buff theory. Strong hydrogen-bonding at the TMAO oxygen, combined with volume exclusion, accounts for the thermodynamics and solvation of TMAO in aqueous urea. As a result, TMAO behaves in a manner that is surprisingly similar to that of hard-spheres. There are two mandatory solvation sites. In plain water, these sites are occupied with water molecules, which are seamlessly replaced by urea, in proportion to its volume fraction. We discuss how this result gives an explanation both for the exceptionally strong exclusion of TMAO from peptide groups and for the experimentally observed synergy between urea and TMAO.

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“…Chemical compounds such as carbohydrates, polyols, amino acids, methylamines or TMAO are known to stabilize the folded state of proteins and therefore are often designated as chemical chaperones, whereas those that favor the unfolded state, such as urea, are known as denaturants. Specifically, TMAO is well-known to act as a protecting osmolyte by stabilizing the folded state of proteins at high pressures (and also high temperatures), thus counteracting their unfolding [42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] . In that sense, TMAO could be viewed as an antagonist to high-pressure protein denaturation.…”

Section: Introductionmentioning

confidence: 99%

Water structure and solvation of osmolytes at high hydrostatic pressure: pure water and TMAO solutions at 10 kbar versus 1 bar

Imoto

Forbert

Marx

2015

Phys. Chem. Chem. Phys.

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Trimethylamine N-oxide (TMAO) is a protecting osmolyte that stabilizes proteins against both temperature and pressure denaturation. Yet, even the solvation of TMAO itself is not well understood beyond ambient conditions. Here, using ab initio molecular dynamics, we analyze how its solvation structure changes upon compressing its ≈0.5 M aqueous solution from 1 bar to 10 kbar. The neat solvent, liquid water compressed to 10 kbar, is analyzed in detail to provide a meaningful gauge for the pressure-induced solvation changes of the solute. Pure water is shown to prefer to keep four H-bonded water molecules in a locally tetrahedral arrangement up to 10 kbar. The eye-catching shape changes of its oxygen-oxygen radial distribution function, where apparently the entire second peak is shifted into the first one, are traced back to about two more water molecules which are squeezed into the tetrahedral voids that are formed in the first shell by the H-bonded water molecules. These additional molecules increase the coordination number of pure water at 10 kbar significantly, but they are definitely not H-bonded to the central water molecule; rather they are its topological second to fourth H-bonded neighbors. The pressure response of TMAO(aq) is distinctly different, although its radial distribution functions do not change much. Under ambient conditions, the negatively charged oxygen site of the solute, which is strongly hydrophilic, predominantly accepts three H-bonds, whereas a roughly equal population of threefold and square-planar fourfold H-bonding is observed at 10 kbar. Moreover, only a negligible contribution of non-H-bonded water molecules is found in the first-shell region of TMAO even at 10 kbar, in contrast to the pressure response of water itself. In the hydrophobic region of TMAO, the solvating water molecules are found to straddle the three methyl groups at ambient pressure, which remains virtually unchanged upon compressing the solution to 10 kbar. Here, the pressure response is an increase from about 17 to 21 water molecules that solvate the methyl groups despite a sizable radial compression of the hydrophobic solvation shell.

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Raman Spectroscopic Signatures of Noncovalent Interactions Between Trimethylamine N-oxide (TMAO) and Water

Cited by 58 publications

References 75 publications

Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies

Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies

Volume Exclusion and H-Bonding Dominate the Thermodynamics and Solvation of Trimethylamine-N-oxide in Aqueous Urea

Water structure and solvation of osmolytes at high hydrostatic pressure: pure water and TMAO solutions at 10 kbar versus 1 bar

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