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Heterogeneous preferential solvation of water and trifluoroethanol in homologous lysozymes.

Arthur EJ, King JT, Kubarych KJ, Brooks CL - J Phys Chem B (2014)

Bottom Line: Cytoplasmic osmolytes can significantly alter the thermodynamic and kinetic properties of proteins relative to those under dilute solution conditions.In pursuit of an accurate and predictive model for explaining biomolecular interactions, we study the averaged structural characteristics of mixed solvents with homologous lysozyme solutes using all-atom molecular dynamics.By observing the time-averaged densities of different aqueous solutions of trifluoroethanol, we deduce trends in the heterogeneous solvent interactions over each protein's surface, and investigate how the homology of protein structure does not necessarily translate to similarities in solvent structure and composition-even when observing identical side chains.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and ‡Biophysics Program, University of Michigan , 930 N. University Avenue , Ann Arbor, Michigan 48109-1055, USA.

ABSTRACT
Cytoplasmic osmolytes can significantly alter the thermodynamic and kinetic properties of proteins relative to those under dilute solution conditions. Spectroscopic experiments of lysozymes in cosolvents indicate that such changes may arise from the heterogeneous, site-specific hydrophobic interactions between protein surface residues and individual solvent molecules. In pursuit of an accurate and predictive model for explaining biomolecular interactions, we study the averaged structural characteristics of mixed solvents with homologous lysozyme solutes using all-atom molecular dynamics. By observing the time-averaged densities of different aqueous solutions of trifluoroethanol, we deduce trends in the heterogeneous solvent interactions over each protein's surface, and investigate how the homology of protein structure does not necessarily translate to similarities in solvent structure and composition-even when observing identical side chains.

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Localsolvent structures near the histidines in simulations of10% TFE v/v. (A) HEWL (yellow) with histidine 15 (orange sticks) issurrounded by TFE (red) and water (blue) isosurfaces. (B) Isosurfacesfor histidine 78 on humLys. Notice that both locations are surroundedby similar ratios of both solvent types. (C) The average number ofempty voxels in the local environment around each histidine at variouscosolvent concentrations as calculated by integrating G(r) functions. The error bars correspond to thestandard deviations of data among the three independent simulationsat each concentration of TFE.
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fig2: Localsolvent structures near the histidines in simulations of10% TFE v/v. (A) HEWL (yellow) with histidine 15 (orange sticks) issurrounded by TFE (red) and water (blue) isosurfaces. (B) Isosurfacesfor histidine 78 on humLys. Notice that both locations are surroundedby similar ratios of both solvent types. (C) The average number ofempty voxels in the local environment around each histidine at variouscosolvent concentrations as calculated by integrating G(r) functions. The error bars correspond to thestandard deviations of data among the three independent simulationsat each concentration of TFE.

Mentions: Although the simulationsof the current study do not reach the level of precision in the workdone by Patel et al., with some margin of error, we can still inferthe relative hydrophobicity of the two histidine sites. By countingthe number of empty voxels around each histidine for each simulation,we obtain the metric shown in Figure 2C, whichshows a systematic increase in the number of waterless voxels withan increase in the concentration of TFE. The probability distributionof empty voxels at various concentrations of TFE is shown in Figure5 of the Supporting Information. The datashows that, beyond the standard deviation of the data between replicas,when the histidines are exposed to higher concentrations of TFE, oneis more likely to find a vacuum-like environment around H15 of HEWLand one is more likely to find a hydrated environment around H78.By the same logic from the studies of Patel et al., we find with highconfidence that H15 is more hydrophobic in an environment of 10% TFEthan one of pure water. These observations may be influenced by thelarge difference in SASA between the residues: 55.1 and 175.1 Å2 for H15 (HEWL) and H78 (humLys) respectively. Figure 2A and B shows a visual reference of the relativesurface area and solvent composition. Interestingly, neither radialdistribution functions nor local concentrations of TFE show any significantdifference between the two histidine sites.


Heterogeneous preferential solvation of water and trifluoroethanol in homologous lysozymes.

Arthur EJ, King JT, Kubarych KJ, Brooks CL - J Phys Chem B (2014)

Localsolvent structures near the histidines in simulations of10% TFE v/v. (A) HEWL (yellow) with histidine 15 (orange sticks) issurrounded by TFE (red) and water (blue) isosurfaces. (B) Isosurfacesfor histidine 78 on humLys. Notice that both locations are surroundedby similar ratios of both solvent types. (C) The average number ofempty voxels in the local environment around each histidine at variouscosolvent concentrations as calculated by integrating G(r) functions. The error bars correspond to thestandard deviations of data among the three independent simulationsat each concentration of TFE.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216199&req=5

fig2: Localsolvent structures near the histidines in simulations of10% TFE v/v. (A) HEWL (yellow) with histidine 15 (orange sticks) issurrounded by TFE (red) and water (blue) isosurfaces. (B) Isosurfacesfor histidine 78 on humLys. Notice that both locations are surroundedby similar ratios of both solvent types. (C) The average number ofempty voxels in the local environment around each histidine at variouscosolvent concentrations as calculated by integrating G(r) functions. The error bars correspond to thestandard deviations of data among the three independent simulationsat each concentration of TFE.
Mentions: Although the simulationsof the current study do not reach the level of precision in the workdone by Patel et al., with some margin of error, we can still inferthe relative hydrophobicity of the two histidine sites. By countingthe number of empty voxels around each histidine for each simulation,we obtain the metric shown in Figure 2C, whichshows a systematic increase in the number of waterless voxels withan increase in the concentration of TFE. The probability distributionof empty voxels at various concentrations of TFE is shown in Figure5 of the Supporting Information. The datashows that, beyond the standard deviation of the data between replicas,when the histidines are exposed to higher concentrations of TFE, oneis more likely to find a vacuum-like environment around H15 of HEWLand one is more likely to find a hydrated environment around H78.By the same logic from the studies of Patel et al., we find with highconfidence that H15 is more hydrophobic in an environment of 10% TFEthan one of pure water. These observations may be influenced by thelarge difference in SASA between the residues: 55.1 and 175.1 Å2 for H15 (HEWL) and H78 (humLys) respectively. Figure 2A and B shows a visual reference of the relativesurface area and solvent composition. Interestingly, neither radialdistribution functions nor local concentrations of TFE show any significantdifference between the two histidine sites.

Bottom Line: Cytoplasmic osmolytes can significantly alter the thermodynamic and kinetic properties of proteins relative to those under dilute solution conditions.In pursuit of an accurate and predictive model for explaining biomolecular interactions, we study the averaged structural characteristics of mixed solvents with homologous lysozyme solutes using all-atom molecular dynamics.By observing the time-averaged densities of different aqueous solutions of trifluoroethanol, we deduce trends in the heterogeneous solvent interactions over each protein's surface, and investigate how the homology of protein structure does not necessarily translate to similarities in solvent structure and composition-even when observing identical side chains.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and ‡Biophysics Program, University of Michigan , 930 N. University Avenue , Ann Arbor, Michigan 48109-1055, USA.

ABSTRACT
Cytoplasmic osmolytes can significantly alter the thermodynamic and kinetic properties of proteins relative to those under dilute solution conditions. Spectroscopic experiments of lysozymes in cosolvents indicate that such changes may arise from the heterogeneous, site-specific hydrophobic interactions between protein surface residues and individual solvent molecules. In pursuit of an accurate and predictive model for explaining biomolecular interactions, we study the averaged structural characteristics of mixed solvents with homologous lysozyme solutes using all-atom molecular dynamics. By observing the time-averaged densities of different aqueous solutions of trifluoroethanol, we deduce trends in the heterogeneous solvent interactions over each protein's surface, and investigate how the homology of protein structure does not necessarily translate to similarities in solvent structure and composition-even when observing identical side chains.

Show MeSH