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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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All three figures above show a reference lysozyme tertiarystructure(yellow) and the residues of the α-helix that are conservedbetween hen egg white and human lysozymes (orange). Since this studyignores buried residues, only the surface-lying residues 107, 108,109, 112, 113, and 114 are shown as sticks. Panel A illustrates theconfiguration of side chains, and panels B and C overlay the proteinwith solvent density averaged from the three replicas at 10% TFE.Even though this helix is completely conserved between the proteins,both in amino acid sequence and relative backbone RMSD, the averagedsolvent densities of water (cyan) and TFE (red) are significantlydifferent at this region. This difference illustrates that neighboringeffects on solvent density from nonidentical residues extend overmany angstroms, and that a region with conserved amino acid sequencedoes not necessarily indicate a region with conserved solvent interactions.
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fig4: All three figures above show a reference lysozyme tertiarystructure(yellow) and the residues of the α-helix that are conservedbetween hen egg white and human lysozymes (orange). Since this studyignores buried residues, only the surface-lying residues 107, 108,109, 112, 113, and 114 are shown as sticks. Panel A illustrates theconfiguration of side chains, and panels B and C overlay the proteinwith solvent density averaged from the three replicas at 10% TFE.Even though this helix is completely conserved between the proteins,both in amino acid sequence and relative backbone RMSD, the averagedsolvent densities of water (cyan) and TFE (red) are significantlydifferent at this region. This difference illustrates that neighboringeffects on solvent density from nonidentical residues extend overmany angstroms, and that a region with conserved amino acid sequencedoes not necessarily indicate a region with conserved solvent interactions.

Mentions: In order to locatethe sources of dissimilar solvent interactions,correlations are segregated by secondary structure type, residue identity,residue similarity, and hydrophobicity. Unfortunately, there are noapparent correlations of the shape of G(r) data between the two types of proteins beyond the variation ofthe data. Of particular interest is the α-helix from residues105 to 114 on HEWL that is entirely conserved between the two lysozymes.An illustration of solvent density at the conserved α-helixis shown in Figure 4, and their correlationsare shown in Figure 3F. There is an average0.11 and 0.03 increase in correlation for water and TFE, respectively,for this particular group, which still falls 0.17 short of the lowestcorrelations of that same group when comparing only one protein toitself in different cosolvents. Comparing homologous residues in thebinding pockets of the proteins yields correlations that are lowerthan the average.


Heterogeneous preferential solvation of water and trifluoroethanol in homologous lysozymes.

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

All three figures above show a reference lysozyme tertiarystructure(yellow) and the residues of the α-helix that are conservedbetween hen egg white and human lysozymes (orange). Since this studyignores buried residues, only the surface-lying residues 107, 108,109, 112, 113, and 114 are shown as sticks. Panel A illustrates theconfiguration of side chains, and panels B and C overlay the proteinwith solvent density averaged from the three replicas at 10% TFE.Even though this helix is completely conserved between the proteins,both in amino acid sequence and relative backbone RMSD, the averagedsolvent densities of water (cyan) and TFE (red) are significantlydifferent at this region. This difference illustrates that neighboringeffects on solvent density from nonidentical residues extend overmany angstroms, and that a region with conserved amino acid sequencedoes not necessarily indicate a region with conserved solvent interactions.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: All three figures above show a reference lysozyme tertiarystructure(yellow) and the residues of the α-helix that are conservedbetween hen egg white and human lysozymes (orange). Since this studyignores buried residues, only the surface-lying residues 107, 108,109, 112, 113, and 114 are shown as sticks. Panel A illustrates theconfiguration of side chains, and panels B and C overlay the proteinwith solvent density averaged from the three replicas at 10% TFE.Even though this helix is completely conserved between the proteins,both in amino acid sequence and relative backbone RMSD, the averagedsolvent densities of water (cyan) and TFE (red) are significantlydifferent at this region. This difference illustrates that neighboringeffects on solvent density from nonidentical residues extend overmany angstroms, and that a region with conserved amino acid sequencedoes not necessarily indicate a region with conserved solvent interactions.
Mentions: In order to locatethe sources of dissimilar solvent interactions,correlations are segregated by secondary structure type, residue identity,residue similarity, and hydrophobicity. Unfortunately, there are noapparent correlations of the shape of G(r) data between the two types of proteins beyond the variation ofthe data. Of particular interest is the α-helix from residues105 to 114 on HEWL that is entirely conserved between the two lysozymes.An illustration of solvent density at the conserved α-helixis shown in Figure 4, and their correlationsare shown in Figure 3F. There is an average0.11 and 0.03 increase in correlation for water and TFE, respectively,for this particular group, which still falls 0.17 short of the lowestcorrelations of that same group when comparing only one protein toitself in different cosolvents. Comparing homologous residues in thebinding pockets of the proteins yields correlations that are lowerthan the average.

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