Water is crucial to structure stability and functional dynamics of biomolecules. Multiple studies are published every year exploring protein and lipid hydration, water states and structure, and hydration effects on biomolecular properties. This paper will review several studies in the aforesaid area that have been carried out in the past few years.
Lipids are the basis for biological membranes – matrixes in which the most important biochemical processes take place. The particular arrangement of lipids contained in such matrixes can be attributed to their interaction with water. A team of scientists from Argentina have investigated water behavior at the phase transition of phospholipid matrixes. The findings appeared in July 2020 in The Journal of Physical Chemistry B. The assessment was carried out by Fourier-transform infrared spectroscopy (FTIR). The study reports changes in molecular organization of confined water during the phase transfer of lipid matrixes. This phenomenon was analyzed at different temperatures and hydration states (relative humidity). Lipid interphases are transitions between the liquid state (liquid crystal) and the solid state (gel) of lipid membranes. Based on the findings, these transitions may be detected from changes in water structure observed by attenuated total reflection FTIR/ATR spectroscopy. It was also shown that different phospholipids associate water at particular modes, resulting in modulations of their structure and hydration. This may further influence the incorporation of amino acids, peptides, and enzymes. Therefore, the scientists believe that water may be used a kind of mirror of the membrane state in biological systems. Putting it another way, it is necessary that studies of biological membranes take into account the water surrounding of such membranes, regarding it as a structural and thermodynamic constituent of their organization.
The phase transition in lipid membranes and water molecule redistribution. Refer to the source
Equally important are studies concerned water-protein interactions. Water forms a hydration layer around proteins, influencing their dynamics, structure, and functions. The role of protein-confined water in allosteric protein regulation is discussed in a study carried out by scientists from the USA and South Korea by using two proteins as an illustration: a homodimeric hemoglobin (HbI) and an A2A adenosine receptor (A2AAR). The research paper was published in June in The Journal of Chemical Physics. For HbI, which consists of two identical monomers – globins, water–protein interactions are seen to influence the dynamics of the protein not only around the protein–water interface but also inside the core of each globule, where dynamic and entropic changes upon ligand binding are associated with protein–water contact dynamics. In the tense state of HbI (deoxy-HbI), its crystal structure contains a cluster of 17 water molecules at the interface between the two monomers, whereas about 6 water molecules are released during oxygen binding. Therefore, the protein state (liganded state or unliganded state) appears to influence the dynamics of water molecules between the monomers, and the water molecules, in their turn, also affect the dynamics of HbI, mediating energy transport and facilitating signaling between and via the globules. The coupled dynamics of protein and water confined between the monomers influences ligand binding and dissociation. The A2A adenosine receptor is a family member of G-protein coupled receptors (GPCR). Given that GPCR currently account for 40% of available drug targets, more detailed insight into their mechanism of activation is of key importance. Similarly to HbI, water molecules trapped deep inside the core region of A2AAR enable the formation of an allosteric network made of water-mediated inter-residue contacts. Extending from the ligand binding pocket to the G-protein binding site, this allosteric network plays key roles in regulating the activity of the receptor.
Structure of deoxy-HbI (a) and of oxy-HbI (b). The figure highlights the hemes (in green), water molecules (red spheres), and some of the residues at the interface between protein monomers in contact with water molecules. For oxy-HbI, a change in the orientation of the residues and a reduced number of water molecules is shown (11 versus 17 in deoxy-HbI). Refer to the source
In another study, water molecule distribution on the lyophilized immunoglobulin G1 (IgG1) surface at different water contents was investigated using computer (MD) simulation.
The paper was published in January 2020 by a team of scientists from the USA and Denmark in Molecular Pharmaceutics. While having a critical role in the stabilization of protein structure, water is a major destabilization factor for the physical and chemical stability of freeze-dried proteins and peptides. For this reason, knowledge of the specifics of water distribution around proteins is essential for understanding numerous phenomena, including drug-receptor interactions. Computer simulation approaches are able to provide information about the distribution concerned at an atomic level. In the study, the distribution of water molecules on the IgG1 surface was shown to be heterogeneous and dependent on the hydration level. Even at relatively high hydration levels, water molecules were found to have limited coverage of the protein surface, forming clusters instead. This continuous monolayer of water molecules only occurs at a hydration level above 30%. In addition, a model to assess water sorption has been developed based on the hydration of different amino acids.
Water molecule distribution on the IgG1 surface (on the left) obtained using molecular dynamics simulation. The protein molecule is highlighted yellow and the water molecule is red and white (red denotes oxygen and white indicates hydrogen). The diagram on the right shows the number of hydrogen bonds of different IgG1 residues with water (hydration). Refer to the source
Water also plays an important part in protein interactions with different solid surfaces. Surface binding of water may be a key factor to influence protein adsorption. Scientists from Switzerland have investigated the hydration of gradient nano-polymer films, showing that the amount and state of water confined to such films influence the adsorption of bovine serum albumin (BSA). BSA adsorption on film surfaces is reduced with increasing hydration times (up to 16 hours). The results of these studies were presented in Colloids and Surfaces B: Biointerfaces. According to the scientists, the observed reduction of BSA adsorption at the surface of gradient polymer films is caused by dipolar oriented water molecules confined in the subsurface, resulting in the generation of a subsurface dipolar field that interacts with the strong dipolar moment of BSA. Exploration of a material’s properties that can contribute to the regulation of protein adsorption at solid-liquid interfaces is a very important subject of research in various areas: from medical applications to the creation of industrial coatings.
The amount of bovine serum albumin adsorbed on gradient polymer films depends on the hydration state (hydration time) of the gradient film. Water confined in the subsurface layers of the film determines the protein-surface interaction. Refer to the source