Protein conformational entropy is not slaved to water

Conformational entropy can be an important element of the thermodynamics of protein functions such as the binding of ligands. The observed role for conformational entropy in modulating molecular recognition by proteins is in opposition to an often-invoked theory for the interaction of protein molecules with solvent water. The solvent slaving model predicts that protein motion is strongly coupled to various aspects of water such as bulk solvent viscosity and local hydration shell dynamics. Changes in conformational entropy are manifested in alterations of fast internal side chain motion that is detectable by NMR relaxation. We show here that the fast-internal side chain dynamics of several proteins are unaffected by changes to the hydration layer and bulk water. These observations indicate that the participation of conformational entropy in protein function is not dictated by the interaction of protein molecules and solvent water under the range of conditions normally encountered

On the nature of aqueous solvation in biological systems

The properties and behavior of water greatly influence biomolecular structure and function, yet many of the subtle effects of water near biomolecular surfaces remain very difficult to study experimentally. The goal of the present work was to develop methodologies to experimentally analyze the water hydrogen bond network near biological molecules and to examine whether the tale of biomolecular solvation was fully encoded in the behavior of this network. An effective two-state hydrogen bonding model was applied to interpret the O-H stretching infrared absorption of water in terms of a mixture of linear and bent hydrogen bonds. Using this simplified model to quantitatively compare temperature excursion infrared spectra of water under various conditions, the effects of ions and nanoconfinement on the water hydrogen bond network were described. Salts were shown to alter the hydrogen bond network behavior of water in correlation with the positions of their constituent ions in the Hofmeister series. Nanoconfinement in reverse micelles was shown to drastically reduce the temperature-sensitivity of the water hydrogen bond network. Under these nanoconfined conditions, bulk water behavior was seen only for a water pool of approximately 15 nm in diameter or larger. These studies indicate that the majority of intracellular water is greatly influenced by ions and charged biomolecular surfaces, and that such water does not behave as bulk water. Water structure near biological small molecules was also examined, and no effect was seen in the influence of solute on solvent for single functional group changes in the small molecules. Despite the lack of difference in the water surrounding these various molecules, the differential coupling of one of their complex aromatic ring vibrational modes to solvent was demonstrated. This coupling was shown to be mediated by hydrogen bonding between peripheral substituents and solvent and was found to depend on the nature and location of hydrogen-bonding substitutions. These findings, taken within the context of other recent work examining the nature of solvation in biological systems, produce a picture of the intracellular environment such that extensive vibrational coupling is possible. The functional implications of such coupling remain to be determined by future investigations

On the nature of aqueous solvation in biological systems

The properties and behavior of water greatly influence biomolecular structure and function, yet many of the subtle effects of water near biomolecular surfaces remain very difficult to study experimentally. The goal of the present work was to develop methodologies to experimentally analyze the water hydrogen bond network near biological molecules and to examine whether the tale of biomolecular solvation was fully encoded in the behavior of this network. An effective two-state hydrogen bonding model was applied to interpret the O-H stretching infrared absorption of water in terms of a mixture of linear and bent hydrogen bonds. Using this simplified model to quantitatively compare temperature excursion infrared spectra of water under various conditions, the effects of ions and nanoconfinement on the water hydrogen bond network were described. Salts were shown to alter the hydrogen bond network behavior of water in correlation with the positions of their constituent ions in the Hofmeister series. Nanoconfinement in reverse micelles was shown to drastically reduce the temperature-sensitivity of the water hydrogen bond network. Under these nanoconfined conditions, bulk water behavior was seen only for a water pool of approximately 15 nm in diameter or larger. These studies indicate that the majority of intracellular water is greatly influenced by ions and charged biomolecular surfaces, and that such water does not behave as bulk water. Water structure near biological small molecules was also examined, and no effect was seen in the influence of solute on solvent for single functional group changes in the small molecules. Despite the lack of difference in the water surrounding these various molecules, the differential coupling of one of their complex aromatic ring vibrational modes to solvent was demonstrated. This coupling was shown to be mediated by hydrogen bonding between peripheral substituents and solvent and was found to depend on the nature and location of hydrogen-bonding substitutions. These findings, taken within the context of other recent work examining the nature of solvation in biological systems, produce a picture of the intracellular environment such that extensive vibrational coupling is possible. The functional implications of such coupling remain to be determined by future investigations