Aqueous TMAO solution under high hydrostatic pressure

Kolling, Inga; Hölzl, Christoph; Imoto, Sho; Alfarano, Serena R.; Vondracek, Hendrik; Knake, Lukas; Sebastiani, Federico; Novelli, Fabio; Hoberg, Claudius; Brubach, Jean‐Blaise; Roy, Pascale Le; Forbert, Harald; Schwaab, Gerhard; Marx, Dominik; Havenith, Martina

doi:10.1039/d1cp00703c

Cited by 7 publications

(11 citation statements)

References 58 publications

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“…In our simulations TMAO increases protein stability in the presence of thermal stress, consistent with its behavior in simulations at high pressure (6,14) or in the presence of denaturants (14,16,21,31). Mechanistically, most TMAO resides in an outer methyl-towards-protein shell at ~5.5 Å, but an oxygen-towards-protein inner shell of TMAO molecules interacts directly with basic side chains (~2.5 Å) at the protein surface, cooperating in a push-pull effect to herd water molecules towards the protein even at high temperature.…”

Section: Discussionsupporting

confidence: 87%

“…S10). Though earlier studies have supported TMAO accepting 3 hydrogen bonds from water (48)(49)(50), a recent study suggests that TMAO can form up to 4 hydrogen bonds with water at high pressure, and we see this effect on a smaller scale in our variable temperature simulations as well (6). The ability of TMAO to form up to four hydrogen bonds with water may be one of the reasons it is able to disrupt water structure and herd more water molecules towards the protein surface, and why the effect quickly saturates with TMAO concentration.…”

Section: Discussionsupporting

confidence: 47%

“…TMAO is characterized by a partial charge separation with the nitrogen and oxygen at the polar end, and its methyl groups at the nonpolar end (Figure 1, top right). The oxygen typically forms three hydrogen bonds with water at normal pressure, and up to four such 'hydrophilic bonds' at high pressure (6), whereas the methyl groups interact with the oxygen of water by 'hydrophobic bonding' (7)(8)(9). While the hydrophilic bonds have a very distinct spectroscopic signature in the terahertz region, the hydrophobic bonds look very similar to bulk water (10).…”

Section: Introductionmentioning

confidence: 99%

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TMAO: Protecting Proteins from Feeling the Heat

Boob¹,

Sukenik²,

Gruebele³

et al. 2022

Preprint

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Osmolytes are ubiquitous in the cell and play an important role in controlling protein stability under stress. The natural osmolyte trimethylamine N-oxide (TMAO) is used by marine animals to counteract the effect of pressure denaturation at large depths. The molecular mechanism of TMAO stabilization against pressure and urea denaturation has been extensively studied, but unlike the case of other osmolytes the ability of TMAO to protect proteins from high temperature has not been quantified. To reveal the effect of TMAO on folded and unfolded protein ensembles and the hydration shell at different temperatures, we study a mutant of the well-characterized, fast-folding model protein B (PRB). We carried out >190 µs in total all-atom simulations of thermal folding/unfolding of PRB at multiple temperatures and concentrations of TMAO. The simulations show increased thermal stability of PRB in presence of TMAO. Partly structured, compact ensembles are favored over the unfolded state. TMAO forms two shells near the protein: an outer shell away from the protein surface alters hydrogen bond lifetimes of water molecules and increases hydration of the protein to help stabilize it; a less-populated inner shell with opposite TMAO orientation closer to the protein surface binds exclusively to basic side chains. The cooperative co-solute effect of the inner and outer shell TMAO has a small number of TMAO molecules ‘herding’ water molecules into two hydration shells at or near the protein surface. The stabilizing effect of TMAO on our protein saturates at 1 M despite higher TMAO solubility, so there may be little evolutionary pressure for extremophiles to produce higher intracellular TMAO concentrations if true in general.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

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TMAO: Protecting Proteins from Feeling the Heat

Boob¹,

Sukenik²,

Gruebele³

et al. 2022

Preprint

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“…X-ray absorption spectroscopy studies by Knierbein et al 50 demonstrated that water is less compressible with increasing TMAO concentration. Fourier transform infrared spectroscopy measurements by Imoto et al 71 and THz spectroscopy measurements by Kolling et al 72 observed a blueshift of the bending/stretching modes associated with the hydrophobic methyl groups on TMAO with increasing pressure, corresponding to increased hydration. However, the modes related to hydrogen bonding to the TMAO NO group were observed to redshift, corresponding with weakened TMAO–water hydrogen bonding with increasing pressure.…”

Section: Introductionmentioning

confidence: 99%

“…However, the modes related to hydrogen bonding to the TMAO NO group were observed to redshift, corresponding with weakened TMAO–water hydrogen bonding with increasing pressure. To gain further atomistic level structural information, these studies are supplemented with ab initio and classical MD to understand the origin of these frequency shifts 71 , 72 . Increased pressure results in a shift from a predominantly three-fold coordinated TMAO oxygen to an increasingly prominent 4-fold coordination.…”

Section: Introductionmentioning

confidence: 99%

The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure

et al. 2022

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Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of high pressure. At the molecular level both TMAO and pressure perturb water structure but it is not understood how they act in combination. Here, we use neutron scattering coupled with computational modelling to provide atomistic insight into the structure of water under pressure at 4 kbar in the presence and absence of TMAO. The data reveal that TMAO resists pressure-induced perturbation to water structure, particularly in retaining a clear second solvation shell, enhanced hydrogen bonding between water molecules and strong TMAO – water hydrogen bonds. We calculate an ‘osmolyte protection’ ratio at which pressure and TMAO-induced energy changes effectively cancel out. Remarkably this ratio translates across scales to the organism level, matching the observed concentration dependence of TMAO in the muscle tissue of organisms as a function of depth. Osmolyte protection may therefore offer a molecular mechanism for the macroscale survival of life in extreme environments.

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Solvation Properties of Neutral Gold Species in Supercritical Water Studied By THz Spectroscopy

Noetzel,

Schienbein,

Forbert

et al. 2024

Angewandte Chemie

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Supercritical water provides distinctly different solvation properties compared to what is known from liquid water. Despite its prevalence deep in the Earth’s crust and its role in chemosynthetic ecosystems in the vicinity of hydrothermal vents, molecular insights into its solvation mechanisms are still very scarce compared to what is known for liquid water. Recently, neutral metal particles have been detected in hydrothermal fluids and proposed to explain the transport of gold species to ore deposits on Earth. Using ab initio molecular dynamics, we elucidate the solvation properties of small gold species at supercritical conditions. The neutral metal clusters themselves contribute enormous THz intensity not because of their intramolecular vibrations, but due to their pronounced electronic polarization coupling to the dynamical supercritical solvent, leading to a continuum absorption up to about 1000 cm‐1 . On top, long‐lived interactions between the gold clusters and solvation water leads at these supercritical conditions to a sharp THz resonance that happens to be close to the one due to H‐bonding in liquid water at ambient conditions. The resulting distinct resonances can be used to analyse the solvation properties of neutral metal particles in supercritical aqueous solutions.

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Aqueous TMAO solution under high hydrostatic pressure

Abstract: Trimethylamine N-oxide (TMAO) is a well-known osmolyte in nature, which deep-sea fish use to stabilize proteins against High Hydrostatic Pressure (HHP). We present a combined ab initio molecular dynamics, force...

Cited by 7 publications

References 58 publications

TMAO: Protecting Proteins from Feeling the Heat

TMAO: Protecting Proteins from Feeling the Heat

The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure

Solvation Properties of Neutral Gold Species in Supercritical Water Studied By THz Spectroscopy

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