Viscosity-Dependent Kinetics of Protein Conformational Exchange: Microviscosity Effects and the Need for a Small Viscogen

Sekhar, Ashok; Latham, Michael P.; Vallurupalli, Pramodh; Kay, Lewis E.

doi:10.1021/jp501583t

Cited by 25 publications

(28 citation statements)

References 36 publications

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“…But also for example for the O 2 escape from respiratory proteins, an inverse correlation between the viscogen molecular weight and its effectiveness at slowing dynamics has been found. 4,13 In a sense, solvent viscosity might be considered just a measure of the concentration of viscogen molecules, and indeed, plotting the averaged time τ 2 against sucrose concentration rather than solvent viscosity reveals a linear dependence up to 40% w/w sucrose concentration (Fig. 6(b)).…”

Section: Merging Experimental and MD Resultsmentioning

confidence: 99%

“…2 Other studies on this topic have measured the viscosity dependence of small ligand dissociation 3,4 or the folding rates of peptides or of entire proteins. [5][6][7][8][9][10][11][12][13][14] Viscosity has an obvious important role in diffusive processes within the cell, but may also have an additional important role in regulating reaction rates and metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Effect of viscogens on the kinetic response of a photoperturbed allosteric protein

Waldauer

Stucki-Buchli

Frey

et al. 2014

The Journal of Chemical Physics

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By covalently binding a photoswitchable linker across the binding groove of the PDZ2 domain, a small conformational change can be photo-initiated that mimics the allosteric transition of the protein.The response of its binding groove is investigated with the help of ultrafast pump-probe IR spectroscopy from picoseconds to tens of microseconds. The temperature dependence of that response is compatible with diffusive dynamics on a rugged energy landscape without any prominent energy barrier. Furthermore, the dependence of the kinetics on the concentration of certain viscogens, sucrose, and glycerol, has been investigated. A pronounced viscosity dependence is observed that can be best fit by a power law, i.e., a fractional viscosity dependence. The change of kinetics when comparing sucrose with glycerol as viscogen, however, provides strong evidence that direct interactions of the viscogen molecule with the protein do play a role as well. This conclusion is supported by accompanying molecular dynamics simulations. By covalently binding a photoswitchable linker across the binding groove of the PDZ2 domain, a small conformational change can be photo-initiated that mimics the allosteric transition of the protein. The response of its binding groove is investigated with the help of ultrafast pump-probe IR spectroscopy from picoseconds to tens of microseconds. The temperature dependence of that response is compatible with diffusive dynamics on a rugged energy landscape without any prominent energy barrier. Furthermore, the dependence of the kinetics on the concentration of certain viscogens, sucrose, and glycerol, has been investigated. A pronounced viscosity dependence is observed that can be best fit by a power law, i.e., a fractional viscosity dependence. The change of kinetics when comparing sucrose with glycerol as viscogen, however, provides strong evidence that direct interactions of the viscogen molecule with the protein do play a role as well. This conclusion is supported by accompanying molecular dynamics simulations. © 2014 AIP Publishing LLC.

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Section: Merging Experimental and MD Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of viscogens on the kinetic response of a photoperturbed allosteric protein

Waldauer

Stucki-Buchli

Frey

et al. 2014

The Journal of Chemical Physics

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“…It should be noted that electrostatic interactions in biomolecular systems can be efficiently modeled by Poisson’s or the Poisson–Boltzmann equation [3, 6, 10, 18, 28, 35, 36]. Experimental and theoretical studies have also indicated that the solvent shear motion can induce protein conformational changes and the solvent viscosity can affect the kinetics of such changes [1, 24, 26, 32, 33, 37–39, 41]. …”

Section: Introductionmentioning

confidence: 99%

Stability of a Cylindrical Solute-Solvent Interface: Effect of Geometry, Electrostatics, and Hydrodynamics

Sun

Zhou

2015

SIAM J. Appl. Math.

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The solute-solvent interface that separates biological molecules from their surrounding aqueous solvent characterizes the conformation and dynamics of such molecules. In this work, we construct a solvent fluid dielectric boundary model for the solvation of charged molecules and apply it to study the stability of a model cylindrical solute-solvent interface. The motion of the solute-solvent interface is defined to be the same as that of solvent fluid at the interface. The solvent fluid is assumed to be incompressible and is described by the Stokes equation. The solute is modeled simply by the ideal-gas law. All the viscous force, hydrostatic pressure, solute-solvent van der Waals interaction, surface tension, and electrostatic force are balanced at the solute-solvent interface. We model the electrostatics by Poisson’s equation in which the solute-solvent interface is treated as a dielectric boundary that separates the low-dielectric solute from the high-dielectric solvent. For a cylindrical geometry, we find multiple cylindrically shaped equilibrium interfaces that describe polymodal (e.g., dry and wet) states of hydration of an underlying molecular system. These steady-state solutions exhibit bifurcation behavior with respect to the charge density. For their linearized systems, we use the projection method to solve the fluid equation and find the dispersion relation. Our asymptotic analysis shows that, for large wavenumbers, the decay rate is proportional to wavenumber with the proportionality half of the ratio of surface tension to solvent viscosity, indicating that the solvent viscosity does affect the stability of a solute-solvent interface. Consequences of our analysis in the context of biomolecular interactions are discussed.

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“…Recent experimental and theoretical studies have indicated that the solvent shear motion can induce protein conformational changes and the solvent viscosity can affect the kinetics of such changes [1, 10, 11, 16, 17, 19–21, 24]. …”

Section: Introductionmentioning

confidence: 99%

Numerical Treatment of Stokes Solvent Flow and Solute–Solvent Interfacial Dynamics for Nonpolar Molecules

et al. 2015

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We design and implement numerical methods for the incompressible Stokes solvent flow and solute-solvent interface motion for nonpolar molecules in aqueous solvent. The balance of viscous force, surface tension, and van der Waals type dispersive force leads to a traction boundary condition on the solute-solvent interface. To allow the change of solute volume, we design special numerical boundary conditions on the boundary of a computational domain through a consistency condition. We use a finite difference ghost fluid scheme to discretize the Stokes equation with such boundary conditions. The method is tested to have a second-order accuracy. We combine this ghost fluid method with the level-set method to simulate the motion of the solute-solvent interface that is governed by the solvent fluid velocity. Numerical examples show that our method can predict accurately the blow up time for a test example of curvature flow and reproduce the polymodal (e.g., dry and wet) states of hydration of some simple model molecular systems.

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Viscosity-Dependent Kinetics of Protein Conformational Exchange: Microviscosity Effects and the Need for a Small Viscogen

Cited by 25 publications

References 36 publications

Effect of viscogens on the kinetic response of a photoperturbed allosteric protein

Effect of viscogens on the kinetic response of a photoperturbed allosteric protein

Stability of a Cylindrical Solute-Solvent Interface: Effect of Geometry, Electrostatics, and Hydrodynamics

Numerical Treatment of Stokes Solvent Flow and Solute–Solvent Interfacial Dynamics for Nonpolar Molecules

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