The effect of complex solvents on the structure and dynamics of protein solutions: The case of Lysozyme in trehalose/water mixtures

GhattyVenkataKrishna, Pavan K.; Carri, Gustavo A.

doi:10.1140/epje/i2013-13014-3

Cited by 13 publications

(6 citation statements)

References 83 publications

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“…This possibly leads to its superior cryo-and lyoprotective properties [130]. MD simulations have been also performed in ternary LSZsugar-water systems at various sugar concentration [131][132][133][134]. More recently, a simulation of a solid state system composed by several LSZ proteins embedded in a low water glassy trehalose matrix has shown the presence of a more tight molecular packing of the proteins, which impairs the formation of large voids present in the dry LSZ glass without sugar [46].…”

Section: Atomistic Levelmentioning

confidence: 99%

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Cordone¹,

Cupane²,

Emanuele

et al. 2015

COC

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Immobilization of proteins and other biomolecules in saccharide matrices leads to a series of peculiar properties that are relevant from the point of view of both biochemistry and biophysics, and have important implications on related fields such as food industry, pharmaceutics, and medicine. In the last years, the properties of biomolecules embedded into glassy matrices and/or highly concentrated solutions of saccharides have been thoroughly investigated, at the molecular level, through in vivo, in vitro, and in silico studies. These systems show an outstanding ability to protect biostructures against stress conditions; various mechanisms appear to be at the basis of such bioprotection, that in the case of some sugars (in particular trehalose) is peculiarly effective.Here we review recent results obtained in our and other laboratories on ternary protein-sugar-water systems that have been typically studied in wide ranges of water content and temperature. Data from a large set of complementary experimental techniques provide a consistent description of structural, dynamical and functional properties of these systems, from atomistic to thermodynamic level.In the emerging picture, the stabilizing effect induced on the encapsulated systems might be attributed to a strong biomolecule-matrix coupling, mediated by extended hydrogen-bond networks, whose specific properties are determined by the saccharide composition and structure, and depend on water content.

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Section: Atomistic Levelmentioning

confidence: 99%

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Cordone¹,

Cupane²,

Emanuele

et al. 2015

COC

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“…TDFSS ,,− of protein solutions even suggested the dramatic slowdown of water mobility by several orders of magnitude. To summarize, although the results of both experiments ,− ,− and computer simulations − suggested that water dynamics are retarded by the protein molecules, quantitative descriptions of the slowdown in hydration water dynamics remain controversial.…”

Section: Introductionmentioning

confidence: 99%

Stochastic Analysis of Molecular Dynamics Reveals the Rotation Dynamics Distribution of Water around Lysozyme

Matsuura

Shirakashi

2022

J. Phys. Chem. B

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Water dynamics is essential to biochemical processes by mediating all such reactions, including biomolecular degeneration in solutions. To disentangle the molecular-scale distribution of water dynamics around a solute biomolecule, we investigated here the rotational dynamics of water around lysozyme by combining molecular dynamics (MD) simulations and broadband dielectric spectroscopy (BDS). A statistical analysis using the relaxation times and trajectories of every single water molecule was proposed, and the two-dimensional probability distribution of water at a distance from the lysozyme surface with a rotational relaxation time was given. For the observed lysozyme solutions of 34–284 mg/mL, we discovered that the dielectric relaxation time obtained from this distribution agrees well with the measured γ relaxation time, which suggests that rotational self-correlation of water molecules underlies the gigahertz domain of the dielectric spectra. Regardless of protein concentration, water rotational relaxation time versus the distance from the lysozyme surface revealed that the water rotation is severely retarded within 3 Å from the lysozyme surface and is nearly comparable to pure water when farther than 10 Å. The dimension of the first hydration layer was subsequently identified in terms of the relationship between the acceleration of water rotation and the distance from the protein surface.

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“…Also, previous simulations were carried out for shorter timescales, at lower temperature and for concentrated solutions and do not cover the study of dynamics at several temperatures. 19,[31][32][33][34] Some of them are intended to explain the cryopreservation and dehydration of protein. In this study, we have focused on the effect of trehalose against thermal denaturation and hence the study was carried out in the high temperature regime and in dilute aqueous solution.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the conundrum of trehalose stabilization

Katyal

Deep

2014

Phys. Chem. Chem. Phys.

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Protein aggregation and loss of protein's biological functionality are manifestations of protein instability. Cosolvents, in particular trehalose, are widely accepted antidotes against such destabilization. Although numerous theories have been promulgated in the literature with regard to its mechanism of stabilization, the present scenario is still elusive in view of the discrepancies existing in them. To this end, we have revisited the conundrum and attempted to rationalize the mechanism by conducting thorough investigation of the effect of trehalose on the native, partially unfolded and denatured states of protein "Lysozyme" by means of molecular dynamic (MD) simulations under different temperature and concentration regimes. Two-dimensional contour plots along with principal component analysis suggest that trehalose molecules offer on-pathway stabilization unaltering the principal direction of protein's motion, although it slows down protein dynamics so that the protein gets trapped in the homogeneous ensemble of conformations closer to the native state. Free energy landscape reveals higher population of native compared to intermediate and denatured states. Delphi results and calculation of the preferential interaction parameter demonstrate that this relative stabilization of the native state can be ascribed to be the consequence of favourable interactions of trehalose with side chains of certain loci on the protein surface encompassing polar flexible residues. Stability of protein results from the observed difference in binding affinity of trehalose for native and denatured states of protein. Our findings are at variance with the common conception of relative destabilization of the denatured state. Rather, we provide evidence for relative stabilization of the native state. This stabilization is due to interplay of protein-trehalose, water-trehalose, water-water, protein-water and trehalose-trehalose interactions.

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The effect of complex solvents on the structure and dynamics of protein solutions: The case of Lysozyme in trehalose/water mixtures

Cited by 13 publications

References 83 publications

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Proteins in Saccharides Matrices and the Trehalose Peculiarity: Biochemical and Biophysical Properties

Stochastic Analysis of Molecular Dynamics Reveals the Rotation Dynamics Distribution of Water around Lysozyme

Revisiting the conundrum of trehalose stabilization

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