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Excluded volume approximation to protein-solvent interaction. The solvent contact model.

ABSTRACT: Important properties of globular proteins, such as the stability of its folded state, depend sensitively on interactions with solvent molecules. Existing methods for estimating these interactions, such as the geometrical surface model, are either physically misleading or too time consuming to be applied routinely in energy calculations. As an alternative, we derive here a simple model for the interactions between protein atoms and solvent atoms in the first hydration layer, the solvent contact model, based on the conservation of the total number of atomic contacts, a consequence of the excluded-volume effect. The model has the conceptual advantage that protein-protein contacts and protein-solvent contacts are treated in the same language and the technical advantage that the solvent term becomes a particularly simple function of interatomic distances. The model allows rapid calculation of any physical property that depends only on the number and type of protein-solvent nearest-neighbor contacts. We propose use of the method in the calculation of protein solvation energies, conformational energy calculations, and molecular dynamics simulations.

SUBMITTER: Colonna-Cesari F

PROVIDER: S-EPMC1280817 | biostudies-other | 1990 May

REPOSITORIES: biostudies-other

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Excluded volume approximation to protein-solvent interaction. The solvent contact model.

Colonna-Cesari F F Sander C C

Biophysical journal 19900501 5

Important properties of globular proteins, such as the stability of its folded state, depend sensitively on interactions with solvent molecules. Existing methods for estimating these interactions, such as the geometrical surface model, are either physically misleading or too time consuming to be applied routinely in energy calculations. As an alternative, we derive here a simple model for the interactions between protein atoms and solvent atoms in the first hydration layer, the solvent contact m ...[more]

PMID: 2340343

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Project description:Changes in excluded volume and contact interaction with the surface of a protein have been suggested as mechanisms for the changes in stability induced by cosolvents. The aim of the present paper is to present an analysis that combines both effects in a quantitative manner. The result is that both processes are present in both stabilizing and destabilizing interactions and neither can be ignored. Excluded volume was estimated using accessible surface area calculations of the kind introduced by Lee and Richards. The change in excluded volume on unfolding, deltaX, is quite large. For example, deltaX for ribonuclease is 6.7 L in urea and approximately 16 L in sucrose. The latter number is greater than the molar volume of the protein. Direct interaction with the protein is represented as the solvent exchange mechanism, which differs from ordinary association theory because of the weakness of the interaction and the high concentrations of cosolvents. The balance between the two effects and their contribution to overall stability are most simply presented as bar diagrams as in Fig. 3. Our finding for five proteins is that excluded volume contributes to the stabilization of the native structure and that contact interaction contributes to destabilization. This is true for five proteins and four cosolvents including both denaturants and osmolytes. Whether a substance stabilizes a protein or destabilizes it depends on the relative size of these two contributions. The constant for the cosolvent contact with the protein is remarkably uniform for four of the proteins, indicating a similarity of groups exposed during unfolding. One protein, staphylococcus nuclease, is anomalous in almost all respects. In general, the strength of the interaction with guanidinium is about twice that of urea, which is about twice that of trimethylamine-N-oxide and sucrose. Arguments are presented for the use of volume fractions in equilibrium equations and the ignoring of activity coefficients of the cosolvent. It is shown in the Appendix that both the excluded volume and the direct interaction can be extracted in a unified way from the McMillan-Mayer formula for the second virial coefficient.

Project description:In this article, we present a classical density functional theory for electrical double layers of spherical macroions that extends the capabilities of conventional approaches by accounting for electrostatic ion correlations, size asymmetry, and excluded volume effects. The approach is based on a recent approximation introduced by Hansen-Goos and Roth for the hard sphere excess free energy of inhomogeneous fluids [J. Chem. Phys. 124, 154506 (2006); Hansen-Goos and Roth, J. Phys.: Condens. Matter 18, 8413 (2006)]. It accounts for the proper and efficient description of the effects of ionic asymmetry and solvent excluded volume, especially at high ion concentrations and size asymmetry ratios including those observed in experimental studies. Additionally, we utilize a leading functional Taylor expansion approximation of the ion density profiles. In addition, we use the mean spherical approximation for multi-component charged hard sphere fluids to account for the electrostatic ion correlation effects. These approximations are implemented in our theoretical formulation into a suitable decomposition of the excess free energy which plays a key role in capturing the complex interplay between charge correlations and excluded volume effects. We perform Monte Carlo simulations in various scenarios to validate the proposed approach, obtaining a good compromise between accuracy and computational cost. We use the proposed computational approach to study the effects of ion size, ion size asymmetry, and solvent excluded volume on the ion profiles, integrated charge, mean electrostatic potential, and ionic coordination number around spherical macroions in various electrolyte mixtures. Our results show that both solvent hard sphere diameter and density play a dominant role in the distribution of ions around spherical macroions, mainly for experimental water molarity and size values where the counterion distribution is characterized by a tight binding to the macroion, similar to that predicted by the Stern model.

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Excluded volume approximation to protein-solvent interaction. The solvent contact model.

Publications

Excluded volume approximation to protein-solvent interaction. The solvent contact model.

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