A molecular dynamics simulation study of the solvent isotope effect on copper plastocyanin

Guzzi, Rita; Arcangeli, Caterina; Bizzarri, Anna Rita

doi:10.1016/s0301-4622(99)00097-6

Cited by 26 publications

(38 citation statements)

References 44 publications

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“…The molecular origins of this enthalpic stabilization are difficult to pinpoint, especially since they cannot be directly measured. D 2 O stabilization of proteins is often attributed to an increase in hydrogen bond strength in heavy water, which is also consistent with the observation that D 2 O reduces protein flexibility . Although a change in solvent hydrogen bond strength would be reflected in a change in enthalpy because there are numerous solvent–solvent, solvent–protein, and protein–protein hydrogen bonds formed during protein folding, there are multiple contributions to the enthalpy of unfolding .…”

Section: Resultssupporting

confidence: 78%

“…D 2 O stabilization of proteins is often attributed to an increase in hydrogen bond strength in heavy water, [18][19][20][21][22] which is also consistent with the observation that D 2 O reduces protein flexibility. 23,24 Although a change in solvent hydrogen bond strength would be reflected in a change in enthalpy because there are numerous solvent-solvent, solvent-protein, and protein-protein hydrogen bonds formed during protein folding, there are multiple contributions to the enthalpy of unfolding. 25 In addition to the enthalpy from hydrogen bond formation and breakage, solvation enthalpy also plays a significant role in protein folding.…”

Section: Origins Of the D 2 O Effectmentioning

confidence: 99%

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Enthalpic stabilization of an SH3 domain by D₂O

Stadmiller

Pielak

2018

Protein Science

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The stability of a protein is vital for its biological function, and proper folding is partially driven by intermolecular interactions between protein and water. In many studies, H O is replaced by D O because H O interferes with the protein signal. Even this small perturbation, however, affects protein stability. Studies in isotopic waters also might provide insight into the role of solvation and hydrogen bonding in protein folding. Here, we report a complete thermodynamic analysis of the reversible, two-state, thermal unfolding of the metastable, 7-kDa N-terminal src-homology 3 domain of the Drosophila signal transduction protein drk in H O and D O using one-dimensional F NMR spectroscopy. The stabilizing effect of D O compared with H O is enthalpic and has a small to insignificant effect on the temperature of maximum stability, the entropy, and the heat capacity of unfolding. We also provide a concise summary of the literature about the effects of D O on protein stability and integrate our results into this body of data.

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Section: Resultssupporting

confidence: 78%

Section: Origins Of the D 2 O Effectmentioning

confidence: 99%

Enthalpic stabilization of an SH3 domain by D₂O

Stadmiller

Pielak

2018

Protein Science

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“…In addition, incoherent neutron scattering measurements, and phosphorescence measurements on some globular proteins have pointed out that D 2 O significantly increases the rigidity of the N‐state, and the damping of structural fluctuations has been assigned to a solvent effect. These findings seem to be in line with results from MD simulations, even though the latter used a D 2 O model constructed by simply doubling the mass of hydrogen atoms in the SPC/E water model …”

Section: Introductionsupporting

confidence: 83%

Effect of heavy water on the conformational stability of globular proteins

Pica

Graziano

2017

Biopolymers

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It is well established from the experimental point of view that the native state of globular proteins is more stable in heavy water than in water. No robust explanation, however, has been provided up to now. The application of the theoretical approach, originally devised to rationalize the general occurrence of cold denaturation, indicates that the magnitude of the solvent-excluded volume effect is slightly smaller in heavy water than in water and cannot explain the observed protein stabilization. The latter has to be due to the strength of protein-water van der Waals attractions which are weaker in heavy water due to the smaller molecular polarizability of D O compared with that of H O molecules. Since protein-water van der Waals attractions occur more in the denatured than in the native state, this contribution leads to a stabilization of the latter through a destabilization of the former.

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“…Overall, the generally short induction time of the D 2 O effects on protein dynamics is more consistent with a change in the solvation properties of heavy water, presumably leading to an increase in the number of intramolecular bonding interactions and additional compaction of the polypeptide. This conclusion was also reached by a molecular dynamics simulation study on plastocyanin where di-minished protein hydration in D 2 O promoted closer packing of the polypeptide and an increase in the number of intraprotein hydrogen bonds (Guzzi et al, 1999). Similarly, Kreshech et al (1965), from the free energy of transfer of model compounds between the two solvents, have concluded that the increased strength of solvent-solvent hydrogen bonds in D 2 O stabilizes the folded state of proteins predominantly through the enhancement of the hydrophobic interaction.…”

Section: Nature Of the Interactions Underlying The D 2 O Effectmentioning

confidence: 69%

Effect of Heavy Water on Protein Flexibility

Cioni

Strambini

2002

Biophysical Journal

176

167

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The effects of heavy water (D(2)O) on internal dynamics of proteins were assessed by both the intrinsic phosphorescence lifetime of deeply buried Trp residues, which reports on the local structure about the triplet probe, and the bimolecular acrylamide phosphorescence quenching rate constant that is a measure of the average acrylamide diffusion coefficient through the macromolecule. The results obtained with several protein systems (ribonuclease T1, superoxide dismutase, beta-lactoglobulin, liver alcohol dehydrogenase, alkaline phosphatase, and apo- and Cd-azurin) demonstrate that in most cases D(2)O does significantly increase the rigidity the native structure. With the exception of alkaline phosphatase, the kinetics of the structure tightening effect of deuteration are rapid compared with the rate of H/D exchange of internal protons, which would then assign the dampening of structural fluctuations in D(2)O to a solvent effect, rather than to stronger intramolecular D bonding. Structure tightening by heavy water is generally amplified at higher temperatures, supporting a mostly hydrophobic nature of the underlying interaction, and under conditions that destabilize the globular fold.

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A molecular dynamics simulation study of the solvent isotope effect on copper plastocyanin

Cited by 26 publications

References 44 publications

Enthalpic stabilization of an SH3 domain by D₂O

Enthalpic stabilization of an SH3 domain by D₂O

Effect of heavy water on the conformational stability of globular proteins

Effect of Heavy Water on Protein Flexibility

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A molecular dynamics simulation study of the solvent isotope effect on copper plastocyanin

Cited by 26 publications

References 44 publications

Enthalpic stabilization of an SH3 domain by D2O

Enthalpic stabilization of an SH3 domain by D2O

Effect of heavy water on the conformational stability of globular proteins

Effect of Heavy Water on Protein Flexibility

Contact Info

Product

Resources

About

Enthalpic stabilization of an SH3 domain by D₂O

Enthalpic stabilization of an SH3 domain by D₂O