TY - JOUR
T1 - Pressure Effects on Protein Hydration Water Thermodynamics
AU - Pattni, Viren
AU - Heyden, Matthias
N1 - Funding Information:
The authors are grateful for support from the School of Molecular Sciences and Research Computing at Arizona State University and for helpful discussions with numerous members of the Cluster of Excellence RESOLV (EXC 1069) funded by the Deutsche Forschungsgemeinschaft (DFG).
Funding Information:
The authors are grateful for support from the School of Molecular Sciences and Research Computing at Arizona State University and for helpful discussions with numerous members of the Cluster of Excellence RESOLV (EXC 1069) funded by the Deutsche Forschungsgemeinschaft (DFG).
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/6/14
Y1 - 2019/6/14
N2 - In this molecular dynamics simulation study, we analyze the impact of increasing hydrostatic pressure on the solvation of protein surfaces. Apart from the increasing volume work required for the formation of the protein solute cavity at high hydrostatic pressures, no significant additional trend is observed for solvation free energy contributions due to the protein-water interactions analyzed here. The latter is the result of approximately canceling pressure-induced changes of enthalpic and entropic solvation free energy contributions, which can be traced back to changes in the hydration of hydrophilic and hydrophobic groups of the protein. The 3D-2PT analysis used here allows for the visualization of local solvation free energy contributions in three dimensions with high spatial resolution. Local solvation free energy contributions per water molecule at hydrophobic surfaces are small but mainly favorable for transfer processes from the gas phase. This does not change considerably with increasing pressure, while the number of hydrating water molecules increases due to increased packing of the hydration shell. The number of hydrating water molecules also increases for hydrophilic protein surfaces, but solvation contributions per water molecule become less favorable with pressure in this case. As a consequence, contributions to the total solvation free energy from interactions between water molecules and hydrophobic surfaces become increasingly relevant at high hydrostatic pressures. Our results provide novel insights into solvent-mediated contributions to the thermodynamic driving force of pressure denaturation of proteins.
AB - In this molecular dynamics simulation study, we analyze the impact of increasing hydrostatic pressure on the solvation of protein surfaces. Apart from the increasing volume work required for the formation of the protein solute cavity at high hydrostatic pressures, no significant additional trend is observed for solvation free energy contributions due to the protein-water interactions analyzed here. The latter is the result of approximately canceling pressure-induced changes of enthalpic and entropic solvation free energy contributions, which can be traced back to changes in the hydration of hydrophilic and hydrophobic groups of the protein. The 3D-2PT analysis used here allows for the visualization of local solvation free energy contributions in three dimensions with high spatial resolution. Local solvation free energy contributions per water molecule at hydrophobic surfaces are small but mainly favorable for transfer processes from the gas phase. This does not change considerably with increasing pressure, while the number of hydrating water molecules increases due to increased packing of the hydration shell. The number of hydrating water molecules also increases for hydrophilic protein surfaces, but solvation contributions per water molecule become less favorable with pressure in this case. As a consequence, contributions to the total solvation free energy from interactions between water molecules and hydrophobic surfaces become increasingly relevant at high hydrostatic pressures. Our results provide novel insights into solvent-mediated contributions to the thermodynamic driving force of pressure denaturation of proteins.
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U2 - 10.1021/acs.jpcb.9b04094
DO - 10.1021/acs.jpcb.9b04094
M3 - Article
C2 - 31198036
AN - SCOPUS:85069973865
SN - 1520-6106
VL - 123
SP - 6014
EP - 6022
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 28
ER -