Statistical Mechanics of Rigid Spheres

Protein-protein interactions are important in many essential biological functions, such as transcription, translation, and signal transduction. Much progress has been made in understanding protein-protein association in dilute solution via experimentation and simulation. Cells, however, contain various macromolecules, such as DNA, RNA, proteins, among many others, and a myriad of non-specific interactions (usually weak) are present between these cellular constituents. In this review article, we describe the important developments in recent years that have furthered our understanding and even allowed prediction of the consequences of macromolecular crowding on protein-protein interactions. We outline the development of our crowding theory that can predict the change in binding free energy due to crowding quantitatively for both repulsive and attractive protein-crowder interactions. One of the most important findings from our recent work is that weak attractive interactions between crowders and proteins can actually destabilize protein complex formation as opposed to the commonly assumed stabilizing effect predicted based on traditional crowding theories that only account for the entropicexcluded volume effects. We also discuss the implications of macromolecular crowding on the population of encounter versus specific native complex.

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“…To calculate the repulsive contribution to the crowding free energy, we adopt the scaled particle theory (SPT) (Reiss et al 1959).…”

Section: Repulsive Contribution To the Crowding Free Energymentioning

confidence: 99%

Protein–protein interactions in a crowded environment

2013

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“…For larger volumes, large terms of alternating sign appear in the expansion eq 27 that make it difficult to use estimated values for the factorial moments in this linear fashion. Equating the excess chemical potential µ ex to the quasi-static work of creating a cavity results in an expression for p 0 in terms of the contact value G(λ) of the solvent density at the surface of the exclusion volume v. For a spherical exclusion volume of radius λ we have: 36,68 …”

Section: F Historical Perspectivementioning

confidence: 99%

“…A number of models of the hydrophobic effect have been developed in the past, 1,2,4,30,31,32,33,34 all having their merits and limitations. 35 One of the most influential models is scaled-particle theory (SPT) 36 and its extension to hydrophobic hydration. 37,38 SPT laid a molecular foundation for surface area models of hydrophobic hydration with macroscopic surface tensions.…”

Section: Introductionmentioning

confidence: 99%

“…The solvation thermodynamics of a hard particle is determined by the excess chemical potential µ ex corresponding to the free energy of its transfer from an ideal gas into the aqueous environment. Statistical mechanics relates this excess chemical potential to the probability p 0 of finding an empty volume v in water, i.e., a cavity of a given size and shape, 36,56 …”

Section: Introductionmentioning

confidence: 99%

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Hydrophobic Effects on a Molecular Scale

et al. 1998

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A theoretical approach is developed to quantify hydrophobic hydration and interactions on a molecular scale, with the goal of insight into the molecular origins of hydrophobic effects. The model is based on the fundamental relation between the probability for cavity formation in bulk water resulting from molecular-scale density fluctuations, and the hydration free energy of the simplest hydrophobic solutes, hard particles. This probability is estimated using an information theory (IT) approach, incorporating experimentally available properties of bulk water -the density and radial distribution function. The IT approach reproduces the simplest hydrophobic effects: hydration of spherical nonpolar solutes, the potential of mean force (PMF) between methane molecules, and solvent contributions to the torsional equilibrium of butane. Applications of this approach to study temperature and pressure effects provide new insights into the thermodynamics and kinetics of protein folding. The IT model relates the hydrophobic-entropy convergence observed in protein unfolding experiments to the macroscopic isothermal compressibility of water. A novel explanation for pressure denaturation of proteins follows from an analysis of the pressure stability of hydrophobic aggregates, suggesting that water penetrates the hydrophobic core of proteins at high pressures. This resolves a long-standing puzzle, whether pressure denaturation contradicts the hydrophobic-core model of protein stability. Finally, issues of "dewetting" of molecularly large nonpolar solutes are discussed in the context of a recently developed perturbation theory approach.

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“…While eq 4 appears as a truncated Maclaurin series, inclusion of higher-order terms shows virtually no improvement for determining the thermodynamic properties of hard spheres. 8 As a non-analytical function, F(R) cannot be adequately represented by a Taylor series.…”

Section: Introductionmentioning

confidence: 99%

Solvation of a Spherical Cavity in Simple Liquids: Interpolating between the Limits

2009

J. Phys. Chem. B

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Dissolution of a solute molecule into a solvent necessitates the creation of a cavity devoid of solvent molecules. The cavity solvation free energy is exactly known at both very small and large length scales, but in between it can only be estimated by various approximations. Guided by simulation results for the solvation of small cavities and density functional theory, we analyze the size dependence of the solvation free energy, contact density of solvent molecules, and the interfacial tension for a spherical cavity in a Lennard-Jones fluid or a system of hard spheres. Unlike cavity formation in the hard-sphere system, a quadratic curvature expansion is insufficient to connect smoothly the exact results in the microscopic and macroscopic limits for the cavity surface tension (or equivalently, the contact solvent density) in Lennard-Jones fluids. Considering the sensitivity of solvation to molecular details at small length scales, we conjecture that, for practical purposes, a heuristic approach may be sufficient to link the thermodynamic limit at large length scales and the exact results of cavity formation at very small length scales.

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Statistical Mechanics of Rigid Spheres

Cited by 1,387 publications

References 14 publications

Protein–protein interactions in a crowded environment

Protein–protein interactions in a crowded environment

Hydrophobic Effects on a Molecular Scale

Solvation of a Spherical Cavity in Simple Liquids: Interpolating between the Limits

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