Solute excluded-volume effects on the stability of globular proteins: A statistical thermodynamic theory

Zhou, Yaoqi; Hall, Carol K.

doi:10.1002/(sici)1097-0282(199602)38:2<273::aid-bip11>3.0.co;2-g

Cited by 23 publications

(18 citation statements)

References 63 publications

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“…Theoretical studies also indicate that steric repulsions can be a major driving force in osmolyte‐induced folding. First, Monte Carlo simulations that treat the D state as a string of small hard spheres show that small solutes could drive folding 44. In addition, these simulations predict that at a given solute concentration, the stabilizing effect should increase with increasing solute size, as we observe.…”

Section: Discussionmentioning

confidence: 52%

Osmolyte-induced changes in protein conformational equilibria

et al. 2000

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Examining solute‐induced changes in protein conformational equilibria is a long‐standing method for probing the role of water in maintaining protein stability. Interpreting the molecular details governing the solute‐induced effects, however, remains controversial. We present experimental and theoretical data for osmolyte‐induced changes in the stabilities of the A and N states of yeast iso‐1‐ferricytochrome c. Using polyol osmolytes of increasing size, we observe that osmolytes alone induce A‐state formation from acid‐denatured cytochrome c and N state formation from the thermally denatured protein. The stabilities of the A and N states increase linearly with osmolyte concentration. Interestingly, osmolytes stabilize the A state to a greater degree than the N state. To interpret the data, we divide the free energy for the reaction into contributions from nonspecific steric repulsions (excluded volume effects) and from binding interactions. We use scaled particle theory (SPT) to estimate the free energy contributions from steric repulsions, and we estimate the contributions from water–protein and osmolyte–protein binding interactions by comparing the SPT calculations to experimental data. We conclude that excluded volume effects are the primary stabilizing force, with changes in water–protein and solute–protein binding interactions making favorable contributions to stability of the A state and unfavorable contributions to the stability of the N state. The validity of our interpretation is strengthened by analysis of data on osmolyte‐induced protein stabilization from the literature, and by comparison with other analyses of solute‐induced changes in conformational equilibria. © 2000 John Wiley & Sons, Inc. Biopoly 53: 293–307, 2000

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Section: Discussionmentioning

confidence: 52%

Osmolyte-induced changes in protein conformational equilibria

et al. 2000

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“…The model presented differs from that of ZH (Zhou and Hall, 1996) primarily in the treatment of the denatured state of the tracer protein. In the present model, the denatured state is assumed to exclude volume to the hard-sphere cosolute as would the convex hull of a Brownian walk, while in the model of Zhou and Hall, the denatured state is assumed to exclude volume to a hard-sphere cosolute as would a chain of tangent hard spheres.…”

Section: Comparison With the Model Of Zhou And Hallmentioning

confidence: 98%

“…On theoretical grounds, volume exclusion would also be expected to affect macromolecular isomerization in general (Minton, 1981(Minton, , 1983 and protein denaturation in particular, as an important example of isomerization. Zhou and Hall (1996) (henceforth referred to as ZH) recently presented a statistical-thermodynamic model for the effect of cosolute excluded volume on the denaturation of proteins. According to their model, high concentrations of larger volume-excluding cosolutes would stabilize proteins against denaturation, while high concentrations of smaller cosolutes would destabilize them.…”

Section: Introductionmentioning

confidence: 99%

Effect of a Concentrated “Inert” Macromolecular Cosolute on the Stability of a Globular Protein with Respect to Denaturation by Heat and by Chaotropes: A Statistical-Thermodynamic Model

Minton

2000

Biophysical Journal

202

165

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An equilibrium statistical-thermodynamic model for the effect of volume exclusion arising from high concentrations of stable macromolecules upon the stability of a trace globular protein with respect to denaturation by heat and by chaotropes is presented. The stable cosolute and the native form of the trace protein are modeled by effective hard spherical particles. The denatured state of the trace protein is represented as an ensemble of substates modeled by random coils having the same contour length but different rms end-to-end distances (i.e., different degrees of compaction). The excess or nonideal chemical potential of the native state and of each denatured substate is calculated as a function of the concentration of stable cosolute, leading to an estimate of the relative abundance of each state and substate, and the ensemble average free energy of the transition between native and denatured protein. The effect of the addition of stable cosolute upon the temperature of half-denaturation and upon the concentration of chaotrope required to half-denature the tracer at constant temperature is then estimated. At high cosolute concentration (Ͼ100 g/l) these effects are predicted to be large and readily measurable experimentally, provided that an experimental system exhibiting a fully reversible unfolding equilibrium at high total macromolecular concentration can be developed.

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“…For example, we know depletion induced attractions promote fiber bundling [6], aggregation of red blood cells [7], and DNA collapse [8]. Reaction kinetics can also be influenced such as in DNA loop formation [5], protein folding [9,10], and modified ligand-protein binding within nuclei [11]. Furthermore, these short-ranged depletion forces have been used to control biological systems, such as form active bundles [12]) and improved polymerase chain reactions [13].…”

Section: Introductionmentioning

confidence: 99%

Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

Shendruk

Bertrand

Harden

et al. 2014

The Journal of Chemical Physics

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Given the ubiquity of depletion effects in biological and other soft matter systems, it is desirable to have coarse-grained Molecular Dynamics (MD) simulation approaches appropriate for the study of complex systems. This paper examines the use of two common truncated Lennard-Jones (Weeks-Chandler-Andersen (WCA)) potentials to describe a pair of colloidal particles in a thermal bath of depletants. The shifted-WCA model is the steeper of the two repulsive potentials considered, while the combinatorial-WCA model is the softer. It is found that the depletion-induced well depth for the combinatorial-WCA model is significantly deeper than the shifted-WCA model because the resulting overlap of the colloids yields extra accessible volume for depletants. For both shifted- and combinatorial-WCA simulations, the second virial coefficients and pair potentials between colloids are demonstrated to be well approximated by the Morphometric Thermodynamics (MT) model. This agreement suggests that the presence of depletants can be accurately modelled in MD simulations by implicitly including them through simple, analytical MT forms for depletion-induced interactions. Although both WCA potentials are found to be effective generic coarse-grained simulation approaches for studying depletion effects in complicated soft matter systems, combinatorial-WCA is the more efficient approach as depletion effects are enhanced at lower depletant densities. The findings indicate that for soft matter systems that are better modelled by potentials with some compressibility, predictions from hard-sphere systems could greatly underestimate the magnitude of depletion effects at a given depletant density.

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Solute excluded-volume effects on the stability of globular proteins: A statistical thermodynamic theory

Cited by 23 publications

References 63 publications

Osmolyte-induced changes in protein conformational equilibria

Osmolyte-induced changes in protein conformational equilibria

Effect of a Concentrated “Inert” Macromolecular Cosolute on the Stability of a Globular Protein with Respect to Denaturation by Heat and by Chaotropes: A Statistical-Thermodynamic Model

Coarse-grained molecular dynamics simulations of depletion-induced interactions for soft matter systems

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