Hydration and Nanoconfined Water: Insights from Computer Simulations

Abstract

The comprehension of the structure and behavior of water at interfaces and under nanoconfinement represents an issue of major concern in several central research areas like hydration, reaction dynamics and biology. From one side, water is known to play a dominant role in the structuring, the dynamics and the functionality of biological molecules, governing main processes like protein folding, protein binding and biological function. In turn, the same principles that rule biological organization at the molecular level are also operative for materials science processes that take place within a water environment, being responsible for the self-assembly of molecular structures to create synthetic supramolecular nanometrically-sized materials. Thus, the understanding of the principles of water hydration, including the development of a theory of hydrophobicity at the nanoscale, is imperative both from a fundamental and an applied standpoint. In this work we present some molecular dynamics studies of the structure and dynamics of water at different interfaces or confinement conditions, ranging from simple model hydrophobic interfaces with different geometrical constraints (in order to single out curvature effects), to self-assembled monolayers, proteins and phospholipid membranes. The tendency of the water molecules to sacrifice the lowest hydrogen bond (HB) coordination as possible at extended interfaces is revealed. This fact makes the first hydration layers to be highly oriented, in some situations even resembling the structure of hexagonal ice. A similar trend to maximize the number of HBs is shown to hold in cavity filling, with small subnanometric hydrophobic cavities remaining empty while larger cavities display an alternation of filled and dry states with a significant inner HB network. We also study interfaces with complex chemical and geometrical nature in order to determine how different conditions affect the local hydration properties. Thus, we show some results for protein hydration and, particularly, some preliminary studies on membrane hydration. Finally, calculations of a local hydrophobicity measure of relevance for binding and self-assembly are also presented. We then conclude with a few words of further emphasis on the relevance of this kind of knowledge to biology and to the design of new materials by highlighting the context-dependent and non-additive nature of different non-covalent interactions in an aqueous nanoenvironment, an issue that is usually greatly overlooked.

Computational Studies on Acetylcholinesterases

“…The functions of water molecules in proteins have attracted a lot of attention [ 40 ]. AChE and its complexes with inhibitors contain a large number of buried water molecules, twice the number per residue typical for globular proteins.…”

“Chameleonic” backbone hydrogen bonds in protein binding and as drug targets

“…Thus, we first determined the existence of heterogeneities in protein hydration properties. To this end, we calculated the water vacating prob-ability, P (N = 0), in small observational (spherical) volumes of radius 4.0 Å [17,18] at each site of interest, with N being the number of water molecules within such volume (P (N = 0) is calculated by computing the number of configurations the observational volume is empty of water molecules divided by the total number of configurations considered along the long MD runs performed). This indicator (which contains an equivalent information as that of normalized water density fluctuations [18]), represents a good measure of local hydrophobicity, since hydrophobiclike surfaces present a higher water vacating probability (larger normalized density fluctuations) than the ones displayed by hydrophilic-like surfaces.…”

Water Behavior at the Phase Transition of Phospholipid Matrixes Assessed by FTIR Spectroscopy

“…Several groups of the lipid molecules act as hydration sites and organize water in different structures that force new H-bond arrangements, such as phosphate groups in which water molecules should orient with its positive ends (protons), carbonyl groups with electron pairs oriented in 120°, and hydrophobic groups (choline and hydrocarbon chains) in which water is forced to reinforce the tetrahedral array of the bulk water. 14,24,25 In this regard, water species have been identified by vibrational sum-frequency generation (VSFG) spectroscopy as water strongly bound to the phosphate groups (ca. 3380 cm −1 ) and weakly bound around the choline groups (ca.…”

“…In a simplified scheme, the tetrahedral array of bulk water should distort or deform according to the nature of the surface next to it. Several groups of the lipid molecules act as hydration sites and organize water in different structures that force new H-bond arrangements, such as phosphate groups in which water molecules should orient with its positive ends (protons), carbonyl groups with electron pairs oriented in 120°, and hydrophobic groups (choline and hydrocarbon chains) in which water is forced to reinforce the tetrahedral array of the bulk water. ,, …”