Protein Denaturation, Zero Entropy Temperature, and the Structure of Water around Hydrophobic and Amphiphilic Solutes

Abstract

The hydrophobic effect plays a key role in many chemical and biological processes, including protein folding. Nonetheless, a comprehensive picture of the effect of temperature on hydrophobic hydration and protein denaturation remains elusive. Here, we study the effect of temperature on the hydration of model hydrophobic and amphiphilic solutes, through molecular dynamics, aiming at getting insight on the singular behavior of water, concerning the zero-entropy temperature, T S , and entropy convergence, T S *, also observed for some proteins, upon denaturation. We show that, similar to hydrocarbons, polar amphiphilic solutes exhibit a T S , although strongly dependent on solute–water interactions, opposite to hydrocarbons. Further, the temperature dependence of the hydration entropy, normalized by the solvent accessible surface area, is shown to be nearly solute size independent for hydrophobic but not for amphiphilic solutes, for similar reasons. These results are further discussed in the light of information theory (IT) and the structure of water around hydrophobic groups. The latter shows that the tetrahedral enhancement of some water molecules around hydrophobic groups, associated with the reduction of water defects, leads to the strengthening of the weakest hydrogen bonds, relative to bulk water. In addition, a larger tetrahedrality is found in low density water populations, demonstrating that pure water has encoded structural information, similar to that associated with hydrophobic hydration. The reversal of the hydration entropy dependence on the solute size, above T S *, is also analyzed and shown to be associated with a greater loss of water molecules exhibiting enhanced orientational order, in the coordination sphere of large solutes. Finally, the source of the differences between Kauzmann’s “hydrocarbon model” on protein denaturation and hydrophobic hydration is discussed, with relatively large amphiphilic hydrocarbons seemingly displaying a more similar behavior to some globular proteins than aliphatic hydrocarbons.

Bridging Gaussian Density Fluctuations from Microscopic to Macroscopic Volumes: Applications to Non-Polar Solute Hydration Thermodynamics

“…The temperature at which the entropies of any two solutes are equal is referred to as their entropy convergence temperature. 7 , 19 , 62 − 66 IGFT accurately reproduces the hydration entropies of all the solutes, although more significant, positive differences are observed for the 3.5 Å solute at elevated temperatures. The positive differences in the entropy appear to compensate for the positive differences in the enthalpy for the 3.5 Å solute ( Figure 8 a), giving rise to a reasonable prediction for the excess chemical potential of this solute over the entire temperature range ( Figure 7 ).…”

Investigating the Ubiquitous Presence of Nanometric Water Films on Surfaces

“…On the one hand, some findings supported both presuppositions above . On the other hand, the structuring and ordering of water molecules is versatile enough to solvate macromolecules, ,, so this should not be regarded or described as a surprising issue . Atomistic simulations of wetting properties and water films on hydrophilic surfaces showed a dependence between relative humidity (RH) and surface free energy .…”

“…The accumulation of molecules such as hydrocarbons and water on surfaces leads to the formation of a thin nanometric interface that mediates and even regulates solid–medium interactions. − This interface results in the so-called set of interfacial properties, , that is, electronic, thermal, physicochemical, and general adhesion, and effectively modifies or indeed establishes the set of surface properties that constitute or give place to the final material structure with the accompanying set of properties. , Thus, far from being an artificial and uncommon system, this nanometric interface regulates the solid–medium interactions that are common in nature and most of those that are encountered as everyday phenomena. , We purposefully speak of a solid–medium interface to emphasize that the solid’s surface might be exposed to vacuum, air, or liquid environments acting as the medium, but the presence of water molecules in the proximity of the surface will play a key role in the restructuring and reorientation of hydrogen bonds, dangling bonds, and OH (hydroxyl) groups . Still, rather than considering this interface part of the constitutive final structure of a solid and its surface, it is common in surface science to refer to it as “contamination” .…”

On the not so anomalous water-induced structural transformations of choline chloride–urea (reline) deep eutectic system

“…Since our main goal is to understand the molecular source of the nonmonotonic behavior of the choline-choline and DES-water coordination, we investigated this force field, hereinafter referred to as OPLS-DA. The main limitation of this force field concerns the dynamics of reline, with the components lying in a sub-diffusive regime in the temperature window 298-328 K. 34 The TIP4P/2005 water model 41 was used in the simulations with water, as it provides a very good description of liquid water and aqueous solutions 42 of OPLS-aa organic molecules.…”