Water in biological systems

Water plays a crucial role in living organisms and it is considered as one of the key factors for the success of Life on Earth. Studies of elementary processes of hydration that intervene in the structure, stabilization, reactions, and transport of biomolecules constitute a very active research theme. Water represents approximately 70% of cell content. Since the living cell medium is highly inhomogeneous and congested, a more homogeneous and rarefied environment is thus favored for disentangled understanding of the roles of cellular components.

A very reductionist approach would consist in isolation of elementary building blocks such as nucleobases, amino acids, sugars, and model molecules complexed with a very small number of water molecules in the gas phase. Experimental in vacuo studies provide accurate snapshots that are directly comparable to high-level quantum predictions. In a more realistic investigation, water molecules in the vicinity of biomolecules would be classified into different categories. Internal, or structural, water molecules are relatively immobile and often essential for the stability and enzymatic activity of globular proteins. Hydration shells of increasing structural disorder surround biomolecules and are sensitive to water–biomolecular surface interactions and crowding conditions. Beyond the outermost hydration shell, bulk water properties dominate but the spatial extension of these hydration shells is often a subject of debate depending on the experimental techniques and conditions.

In recent years, many experimental tools have provided a rich but still incomplete picture of the effects of water on structure, dynamics, and activity of biomolecular systems. X-Ray crystallography, solution or solid-state NMR, dielectric spectroscopy, inelastic neutron scattering, fluorescence of surface residues, and more recently 2D infrared spectroscopy have been used to explore the ordering of water around biomolecules and cooperative insertion of water into hydrophobic cavities over a wide range of temperatures. The coupling of motions between water and biomolecules has been studied in time scales ranging from femtosecond to microsecond. Terahertz spectroscopy has been used to directly probe hydration dynamics around proteins and determine the width of the dynamical hydration layers. Quantitative simulations that are essential for understanding the stability and enzymatic activity of globular proteins, molecular recognition and other functions of membrane channels, and designing new drugs capable of enhancing or blocking biochemical pathways cannot underestimate the ubiquitous presence of water. Since hydration layers can contain an extremely large number of water molecules, full high-level quantum modelling is unfortunately not feasible. Explicit and implicit representations of water molecules, and their combinations, are thus widely used, along with the interplay between quantum molecular dynamics and experimental approaches.

This partial themed issue contains experimental and theoretical investigations that offer a wide overview concerning the role of water in biomolecular structures and functions. Cui (DOI: 10.1039/c002414g) considers in a single-molecule experiment the hydration and dehydration processes that regulate the single- and double-stranded supramolecular structures of DNA. This leads him to suggest that water acts as a selector in the natural selection of prebiotic macromolecules towards self-assembling systems. The self-organizing structure of DNA may have been selected in an aqueous environment as a step in a possible roadmap towards self-replicating macromolecules and further primitive living species.

Two microwave spectroscopy studies by Caminati et al. (DOI: 10.1039/c003513k and DOI: 10.1039/c003649h) conducted under isolated and very low-temperature conditions illustrate a state-of-the-art reductionist gas-phase approach. The extremely precise determination of hydrated model-system complex structures shows how a single water molecule influences trans and cis peptide bond configurations. At room temperature, peptide structures are no longer as well-defined. A DFT-based molecular study by Gaigeot (DOI: 10.1039/c003485a) interprets infrared spectroscopic data of a protected dipeptide. This quantitatively shows how conformational equilibria are encountered in the liquid phase. The structure of water, and more generally of liquids, in the presence of biomolecules is still much debated. The respective roles of enthalpy and entropy in the presence of hydrophobic and hydrophilic groups are not entirely understood. The aggregation and self-assembling processes of water–alcohol mixtures are considered by Dougan et al. (DOI: 10.1039/c003407j) at low temperature and concern the denaturation of proteins induced by temperature and pressure conditions. Conserved water molecules are often found in the active site of enzymes. Quantum chemistry and molecular dynamics calculations are valuable tools for deciphering the mechanisms involved in enzymatic activity. Alagona et al. (DOI: 10.1039/c003999c) quantitatively explore the catalytic effect of explicit water molecules on keto–enol tautomerism in the enolpyruvate model system.

High-resolution solid-state NMR with isotopic substitution provides an understanding of hydrogen bond formation. The effect of the degree of hydration, starting from a dry situation, on the formation of secondary structures such as α-helices and β-sheets is investigated in solid poly-L-lysine in the presence of acids by Dos et al. (DOI: 10.1039/c002730h). NMR can also be applied to the monitoring of motion and exchange kinetics of water molecules as a function of time. Modig et al. (DOI: 10.1039/c002970j) compare the situation of the aqueous solvent in conventional proteins to that encountered in the case of antifreeze proteins preventing ice formation at sub-zero temperatures. They investigate, on a microsecond time scale, the exchange of water molecules between structured, internally buried states and the bulk water state. While there is no evidence of ice-like behavior for the bulk solvent, internal water molecules exhibit an ice-like structure. Hydrogen bond rearrangement in the water molecule network influences the structure and thus the function of biomolecules in aqueous solutions. It can be monitored through terahertz spectroscopy since terahertz signals penetrate thick layers and their absorption is sensitive to hydration and temperature. Kawaguchi et al. (DOI: 10.1039/b927397b) investigate the low-frequency dynamics of bacteriorhodopsin at low temperatures and compare their results to those obtained from inelastic neutron scattering.

Hydrogen bonding properties of water depend upon temperature. In order to suppress freezing and still investigate proteins in liquid water at very low temperatures (−120 °C), Reátegui and Aksan (DOI: 10.1039/c003517c) study model proteins that are confined in silica nanoporous matrices. They demonstrate that the modification of the hydrogen bonding properties of water influences the structure of the confined proteins.

Water and small solutes must be transported through cell membranes. Aquaglyceroporins are channel proteins facilitating the diffusion of water as well as glycerol. Aponte-Santamaría et al. (DOI: 10.1039/c004384m) use molecular dynamics simulations to investigate the subtleties of transport mechanisms of the aquaglyceroporin for the Plasmodium falciparum parasite responsible for malaria. This may turn out to be very useful for designing new drugs against this scourge. Water has been considered as playing an important role in general anesthesia. Willenbring et al. (DOI: 10.1039/c003573d) have revisited the problem of the allosteric opening and closing of an ionic channel of the acetylcholine receptor under the influence of a volatile anesthetic. Molecular dynamics simulations again provide a quantitative answer to this long-standing question. Anesthetic action involves water that mediates the interactions between receptor subunits and alters protein dynamics, but is not associated with clathrate formation around anesthetics as originally proposed by Pauling.

Overall, this issue covers a wide range of studies concerning water that exhibit so many facets in its interactions with biomolecular systems. Although many problems remain unsolved and conflicting results are still sometimes obtained from different approaches, great progress has been achieved by means of combined spectroscopic techniques and modeling in the understanding of physicochemical and biochemical properties of water. This becomes more and more indispensable in the search for new drugs as well as for understanding biological and medical phenomena.

Seong Keun Kim, Department of Chemistry and WCU Department of Biophysics and Chemical Biology, Seoul National University, Korea

Taekjip Ha, Department of Physics, University of Illinois at Urbana Champaign, USA; Howard Hughes Medical Institute, USA; WCU Department of Biophysics and Chemical Biology, Seoul National University, Korea

Jean-Pierre Schermann, Laboratoire de Physique des Lasers, Université Paris 13, France; WCU Department of Biophysics and Chemical Biology, Seoul National University, Korea

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