Molecular dynamics study of solvation in urea water solution

Kuharski, Robert A.; Rossky, Peter J.

doi:10.1021/ja00332a005

Cited by 178 publications

(155 citation statements)

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“…However, spectroscopic data suggest that urea has little effect on water structure, as O-D stretching frequencies in HDO are unaffected by urea. 25 This conclusion is supported by molecular dynamics simulations which show that urea has little effect on the O-O radial distribution function, 26,27 and by the observation that urea and water mix as nearly ideal solutions. 20 Consequently, urea's diminution of the hydrophobic effect cannot be attributed to urea's action as a structure breaker.…”

Section: Hydrophobic Contributionsmentioning

confidence: 87%

Urea effects on protein stability: Hydrogen bonding and the hydrophobic effect

Zou

Habermann-Rottinghaus

1998

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The effects of urea on protein stability have been studied using a model system in which we have determined the energetics of dissolution of a homologous series of cyclic dipeptides into aqueous urea solutions of varying concentration at 25 degrees C using calorimetry. The data support a model in which urea denatures proteins by decreasing the hydrophobic effect and by directly binding to the amide units via hydrogen bonds. The data indicate also that the enthalpy of amide hydrogen bond formation in water is considerably higher than previously estimated. Previous estimates included the contribution of hydrophobic transfer of the alpha-carbon resulting in an overestimate of the binding between urea and the amide unit of the backbone and an underestimate of the binding enthalpy.

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Section: Hydrophobic Contributionsmentioning

confidence: 87%

Urea effects on protein stability: Hydrogen bonding and the hydrophobic effect

Zou

Habermann-Rottinghaus

1998

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“…enthalpy of solution of the acid and mode: is measured in the pure base Due to the ability of urea to act as a strong protein denaturant considerable theoretical and experimental research has been focused on aqueous urea solutions (1)(2)(3)(4)(5). In particular, Somsen and co-workers (3)(4)(5) have studied the thermodynamic enthalpies of aqueous solutions of urea and methyl-substituted ureas.…”

Section: Introductionmentioning

confidence: 99%

Solvation of urea and methyl-substituted ureas by water and DMF

Spencer¹,

Hovick²

1988

Can. J. Chem.

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. Can. J. Chem. 66, 562 (1988).The hydrogen bond enthalpies of urea and methyl-substituted ureas with water and DMF have been determined by the pure-base calorimetric method. Transfer enthalpies between water and DMF have been calculated for dilute solutions of the ureas according to a previously developed model. The first solvation sphere of urea in water consists of five water molecules. Solvation spheres are given for other methyl-substituted ureas in water and DMF.

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“…Most molecular dynamics (MD) simulations have focused on simple model systems and small peptides for which exhaustive sampling of the conformations can be performed (7,(15)(16)(17)(19)(20)(21)(22)(23). In the small peptides, almost all of the backbone and the side chains are solvent exposed.…”

mentioning

confidence: 99%

Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding

Hua

Zhou

Thirumalai

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

496

621

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The mechanism of denaturation of proteins by urea is explored by using all-atom microseconds molecular dynamics simulations of hen lysozyme generated on BlueGene/L. Accumulation of urea around lysozyme shows that water molecules are expelled from the first hydration shell of the protein. We observe a 2-stage penetration of the protein, with urea penetrating the hydrophobic core before water, forming a ''dry globule.'' The direct dispersion interaction between urea and the protein backbone and side chains is stronger than for water, which gives rise to the intrusion of urea into the protein interior and to urea's preferential binding to all regions of the protein. This is augmented by preferential hydrogen bond formation between the urea carbonyl and the backbone amides that contributes to the breaking of intrabackbone hydrogen bonds. Our study supports the ''direct interaction mechanism'' whereby urea has a stronger dispersion interaction with protein than water.denaturing mechanism ͉ dry globule ͉ molecular dynamics ͉ preferential binding ͉ lysozyme unfolding

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Molecular dynamics study of solvation in urea water solution

Cited by 178 publications

References 1 publication

Urea effects on protein stability: Hydrogen bonding and the hydrophobic effect

Urea effects on protein stability: Hydrogen bonding and the hydrophobic effect

Solvation of urea and methyl-substituted ureas by water and DMF

Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding

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