Dynamics Of Hydration Water Research Articles

Effect of trehalose on protein cryoprotection: Insights into the mechanism of slowing down of hydration water.

We study, with molecular dynamics simulations, a lysozyme protein immersed in a water-trehalose solution upon cooling. The aim is to understand the cryoprotectant role played by this disaccharide through the modifications that it induces on the slow dynamics of protein hydration water with its presence. The α-relaxation shows a fragile to strong crossover about 20° higher than that in the bulk water phase and 15° higher than that in lysozyme hydration water without trehalose. The protein hydration water without trehalose was found to show a second slower relaxation exhibiting a strong to strong crossover coupled with the protein dynamical transition. This slower relaxation time importantly appears enormously slowed down in our cryoprotectant solution. On the other hand, this long-relaxation in the presence of trehalose is also connected with a stronger damping of the protein structural fluctuations than that found when the protein is in contact with the pure hydration water. Therefore, this appears to be the mechanism through which trehalose manifests its cryoprotecting function.

Slow dynamics of supercooled trehalose hydration water in comparison with bulk water

Trehalose aqueous solutions are relevant in many technological applications, for example in cryopreservation of biomolecules. It is known that the presence of this disaccharide is able to slow down the dynamics of nearby water molecules and to modify their spatial rearrangement, nevertheless, a complete understanding of the properties of water-trehalose solutions and of trehalose cryoprotective properties is still lacking. Here we discuss recent molecular dynamics simulation results of water-trehalose solutions, performed at different temperatures upon cooling, and we compare the results with the behavior of the bulk phase. In particular we focus on the dynamical properties of hydration water, i.e., the water molecules in the hydration shell of the disaccharide. Hydration water shows a sub-diffusive behavior with respect to bulk water, the same structural relaxation typical of glass formers liquids, albeit slightly slower than in the bulk, and an additional relaxation process at longer timescales completely absent in the bulk. The analysis of hydrogen bond autocorrelation functions allows to connect the structural and long relaxation processes of hydration water to the dynamics of two distinct population of hydrogen bonds in the system, the water-water and water-trehalose hydrogen bonds.

Effects of sodium and calcium chloride ionic stresses on model yeast membranes revealed by molecular dynamics simulation

As efforts to move a renewable economy grow, it will be necessary to make use of microbial conversion strategies for the production of novel materials or the upgrading of waste to high-value products. One critical technical challenge currently limiting waste upgrading remains the difficulty in obtaining single-pot conversion techniques where physical, chemical, and biological conversion are performed in a single step. To overcome this challenge, a detailed understanding of how different stresses impact microbial membrane stability will be necessary. Using all-atom molecular dynamics simulations, we examine the impacts of moderate concentrations of NaCl and CaCl2on a model yeast plasma membrane. Weak, though statistically significant, changes in membrane morphology and dynamics functions are observed that are consistent with swelling and stiffening. Additionally, an examination of the ion-lipid contacts and the behavior of water at the water-membrane interface suggests that the impacts of these common salts may, in part, be mediated through changes to water-membrane hydrogen-bonding and hydration water dynamics.

Effect of Alzheimer's Disease Causative and Protective Mutations on the Hydration Environment of Amyloid-β.

This study investigates the local structure and dynamics of hydration water around the intrinsically disordered protein amyloid-β (Aβ) and its Alzheimer's disease causative N-terminus mutants, i.e., A2V, Taiwan (D7H), Tottori (D7N), and English (H6R), and the protective A2T mutant via atomistic MD simulations. The effect of mutations on the hydration environment around different domains of this protein is evaluated through the surface distribution function, tetrahedral order parameter, and the survival probability of the water molecules within the hydration shell. The water density around the hydrophobic hp1 (17-21) domain is found to be higher for the A2T mutant as compared to the wild-type Aβ and its selected causative mutants. The average tetrahedral order parameter of water molecules around the hydrophobic hp1 (17-21) domain shows that water molecules are less ordered around the A2V, Taiwan, Tottori, and English mutants and more ordered around the A2T mutant than those of the wild-type protein. The survival probability decays rapidly for the A2V, Taiwan, Tottori, and English mutants, while it is comparatively slower for the protective A2T mutant. These results exhibit different hydration environments for the causative and protective mutants highlighting the differential roles of charge and hydrophobicity.

Slow dynamics of supercooled hydration water in contact with lysozyme: examining the cage effect at different length scales

ABSTRACT We study by computer simulation the dynamics of hydration water in solution with lysozyme upon approaching the glassy state of water. We calculate the self-density correlation function at different wavelengths to test the Mode Coupling Theory (MCT) of glassy dynamics at different length scales. The results show a strict and clear relation of the behaviour of the structural relaxation with the cage effect. We find a good agreement with the predictions of the MCT in the short and medium scale range, while at increasing length scales the interaction of water molecules with the protein's substrate induces deviations from the MCT behaviour, as found in previous studies. Besides at low temperatures the slow dynamics deviates from MCT due to hopping processes, similar to the bulk, as witnessed by a crossover from a fragile behaviour to a strong behaviour. We show that this deviation is evident at all length scales. Interestingly, we find that in the fragile region the confining cage decreases in radius with temperature while in the strong region it appears stable.

In-Operando Changes of the Cation Exchange Membrane in CO2 electrolyzers

CO2 electrolysis provides a promising solution for reducing CO2 concentration levels in the atmosphere and for decarbonizing current CO2 sources. Through CO2 electrolysis, we can synthesize syngas, formic acid, and other useful hydrocarbon feedstocks [1] for carbon-neutral fuels, creating a cyclic consumption of hydrocarbons. A critical limitation of industrializing current CO2 electrolyzer designs is understanding the mass and ionic transport effects of the reactants and products across the membrane-electrode assembly [1,2]. These effects are directly dependent on the operating conditions and reduce cell performance [1]. Membrane hydration is an important parameter that significantly affects cell performance and optimum performance can be achieved by supplying humidified CO2 gas supply at the cathode, as evident in fuel cell technologies [3]. In this study, we investigated the impact of humidified CO2 gas supply on cell performance and correlated it with mass transport effects causing changes in the cation exchange membrane (CEM). We operated a CEM CO2 electrolyzer with varied cathode gas inlet relative humidity (RH) to study the performance change at various current densities while simultaneously using synchrotron X-ray radiography to quantify membrane hydration changes and water dynamics. These results were coupled with electrochemical impedance spectroscopy (EIS) data, which gave us the high frequency resistance (HFR) highlighting the ohmic losses present in the membrane at various RH conditions. Similar work on other electrochemical devices (fuel cells [4] and water electrolyzers [5]) has shown the relationship between cell performance and changes in membrane hydration and transport resistance. Significant improvement in cell performance was observed as the cathode inlet RH increased. This improvement is a direct result of increased membrane hydration. Furthermore, EIS data exhibited a significant decrease in HFR as RH increased, indicative of lower ionic transport resistance across the membrane. As the electrolyzer is operated at various current densities, the through plane visualizations of the CEM provide insight into the relative changes in the membrane. Mass transport phenomena have a significant effect on cell performance at elevated current densities, which is evident by in-operando membrane hydration changes and membrane ohmic losses. From our observations, the humidification of CO2 gas supply has a significant effect on cell performance. We believe this knowledge can be translated into substantially improving the performance of CO2 electrolyzers for industrial-scale implementation.

Dynamics of hydration water in gelatin and hyaluronic acid hydrogels.

We employed broadband dielectric spectroscopy (BDS), for the investigation of the water dynamics in partially hydrated hyaluronic acid (HA), and gelatin (Gel), enzymatically crosslinked hydrogels, in the water fraction ranges [Formula: see text]. Our results indicate that at low hydrations ([Formula: see text]), where the dielectric response of the hydrogels is identical during cooling and heating, water plasticizes strongly the polymeric matrix and is organized in clusters giving rise to [Formula: see text]-process, secondary water relaxation and to an additional slower relaxation process. This later process has been found to be related with the dc charge conductivity and can be described in terms of the conduction current relaxation mechanism. At slightly higher hydrations, however, always below the hydration level where ice is formed during cooling, we have recorded in HA hydrogel a strong water dielectric relaxation process, [Formula: see text], which has Arrhenius-like temperature dependence and large time scale resembling relaxation processes recorded in bulk low density amorphous solid water structures. This relaxation process shows a strong-to-fragile transition at [Formula: see text]C and our data suggest that the VTF-like process recorded at [Formula: see text]C is controlled by the same molecular process like long range charge transport. In addition, our data imply that the crossover temperature is related with the onset of structural rearrangements (increase in configurational entropy) of the macromolecules. In partially crystallized hydrogels ([Formula: see text]) HA exhibits at low temperatures the ice dielectric process consistent with the bulk hexagonal ice, whereas Gel hydrogel exhibits as main low temperature process a slow relaxation process that refers to open tetrahedral structures of water similar to low density amorphous ice structures and to bulk cubic ice. Regarding the water secondary relaxation processes, we have shown that the [Formula: see text]-process and the [Formula: see text] process are activated in water hydrogen bond networks with different structures.

Unusual dynamics of hydration water around motor proteins with long-ranged hydrodynamic fluctuations

A fluctuation-driven dynamic model is formulated to study the translational diffusion of water molecules around the surface of motor proteins under the combined influence of the thermal fluctuations and the external active forces. The dynamics of such a system, explored within the tenets of generalized Langevin equation is captured by two different models that characterizes the interplay between the active and thermal fluctuations. The results establish that hydration water dynamics is primarily super-diffusive when the active conformational fluctuations of motor proteins outweigh the random thermal fluctuations in the environment. The conformational fluctuations of protein disrupts the hydrogen bonded network of water and enhances its dynamics in a homogeneous environment. First passage time distribution and the survival probability are evaluated from the effective Fokker–Planck equation for both models under two different boundary conditions. The results depict an asymmetric unimodal distribution of FPTD with curves of varying amplitudes obtained at definite intervals of time for two different models. The FPT distribution of water molecules displays broad peaks with a lower amplitude for the hydration layers of increasing thickness. The survival probability of hydration water molecules exhibits a stretched exponential decay for both models with a faster decay rate for the super-diffusive dynamics as compared to the sub-diffusive motion. The water molecule displays a longer residence time within the hydration layer bounded by an absorbing–reflecting boundary as compared to an absorbing–absorbing one.

Disentangling Polymer Network and Hydration Water Dynamics in Polyhydroxyethyl Methacrylate Physical and Chemical Hydrogels

The cross-linker nature and water content may impact the microscopic dynamics of hydrogels components and thus their properties in applications such as drug delivery and water confinement. To inves...

Glassy dynamics of water at interface with biomolecules: A Mode Coupling Theory test

We study the slow dynamics of hydration water upon cooling in two different biological aqueous solutions, one containing a molecule of lysozyme and another with trehalose molecules. In particular we test if the glassy behaviour of these solutions fulfils the predictions of the popular Mode Coupling Theory of glassy dynamics. In particular we test the Time Temperature Superposition Principle and the matching of the exponents of the theory. Our results confirm that this theory is able to describe the dynamical behaviour of supercooled water also in non ideal cases as the ones under investigation in the region of mild supercooling.

Water in the hydrated protein powders: Dynamic and structure.

It is not an understatement to say that the interplay between water and protein is a fundamental aspect of life. The vitality of an organism depends on the functionality of its biological machinery, and this, in turn, is mediated in water. Yet, we understand surprisingly little about the nature of the interface between bulk water and the protein. On the one hand, we know that the nature of the bulk water is dominated by the existence of H-bonding and H-bonded networks. On the other hand, the protein surface, where much of the bioactivity is centered, is a complex landscape of hydrophilic and hydrophobic elements. So how does the interface between these two entities work and how do they influence each other? The question is important because if one understands how a particular protein interface influences the dynamics of the water, it then becomes an easily accessible marker for similar behavior in other protein systems. The dielectric relaxation of hydrated proteins with different structures, lysozyme, collagen, and phycocyanin, has been reviewed in this paper. The dynamics of hydrated water was analyzed in terms of orientation and the ionic defect migration model. This approach enables to characterize the microscopic relaxation mechanism of the dynamics of hydration water on the different structures of the protein. In addition, our model is also capable of characterizing not only hydrated proteins but also polymer-water systems.

Structure and Dynamics of Collagen Hydration Water from Molecular Dynamics Simulations: Implications of Temperature and Pressure.

Dynamics of water molecules in hydrated collagen plays an important role in determining the structural and functional properties of collagenous tissues. Experimental results suggest that collagen-bridging water molecules exhibit dynamic and thermodynamic properties of one-dimensional ice. However, molecular dynamics (MD) studies performed to date have failed to identify icelike water bridges. It has been hypothesized that this discrepancy is due to the experimental measurements and computational MD analysis having been performed on very different systems: complete tissues with large-scale collagen fiber assemblies and individual tropocollagen fragments, respectively. In this work, we explore ways of emulating a tissuelike macromolecular environment in MD simulations of hydrated collagen without increasing the size of the system to computationally prohibitive levels. We have investigated the effects of temperature and pressure on the dynamics of a small hydrated tropocollagen fragment. The occupancy and bond energies of interchain hydrogen bonds were relatively insensitive to temperature, suggesting that they play a key role in the stability of the collagen triple helix. The lifetimes of water bridges lengthened with decreasing temperature, but even at 280 K, no bridging water molecules exhibited icelike dynamics. We discuss the implications of these findings for the ability to emulate tissuelike conditions in hydrated collagen.

Functional Water Dynamics in Rhodopsin Using Solid‐State Deuterium NMR Spectroscopy

G‐protein‐coupled receptors (GPCRs) are the largest family of cell membrane‐bound proteins that detect extracellular stimuli and transduce signals to activate intracellular functions. Drugs that target GPCRs also account for about 27% of the global market share of therapeutic drugs, with aggregated sales for 2011–2015 of ca. US $890 billion [1]. Hydration is essential for protein tertiary folding and activity, and therefore knowledge of hydration water dynamics is vital for understanding the GPCR activation mechanism [2]. We studied rhodopsin hydration as a prototype for GPCRs, where the role of water in the rhodopsin activation mechanism has been recently explored using quasi‐elastic neutron scattering (QENS) methods [3]. We developed methods for generating powdered samples, notable for exceptionally high protein content while retaining photochemical functionality. The powdered GPCR samples are suitable for biophysical experiments to study the dynamic process of rhodopsin activation [4], where the protein is hydrated using vapor phase absorption in a controlled manner. We propose that the internal protein dynamics (β‐fluctuations) are coupled to the solvent shell, while large‐scale protein domain motions (α‐fluctuations) are coupled to the bulk solvent. To test our hypothesis of functional water interactions, we studied rhodopsin hydration shell dynamics using solid‐state 2H NMR spectroscopy at various hydration levels and temperatures [5]. From the spectral features at 200 K, we identified two dynamically distinguishable protein hydration regions. The broad quadrupolar splitting at approximately 180 kHz is due to bulk water; however, the anisotropic narrow component is a result of water molecules dynamically perturbed by rhodopsin. Additional solid‐state 2H NMR relaxation investigations of molecular dynamics of the rhodopsin‐bound water shell are in progress. Our future focus is on a comparative study of water dynamics in the light activated state and the dark state of the visual photoreceptor.Support or Funding InformationThis work was supported by the NIH (EY026041 and EY012049) and the NSF (MCB 1817862).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Slow dynamics of hydration water and the trehalose dynamical transition

We present results from molecular dynamics simulations of a solution of water and trehalose, a cryoprotecting disaccharide, upon cooling. We focus our attention on both the dynamics of hydration water and of the trehalose. Hydration water presents two slow relaxations. One is the α relaxation typical of glass formers and the second one is a long relaxation that was also found in proteins hydration water and appears coupled to the movement of the surface of trehaloses. Below 280 K trehalose aggregates and upon further cooling we find a dynamical transition for the trehalose aggregate at around 250 K similar to the well known Protein Dynamical Transition. When this transition happens the long relaxation time has a dynamical crossover. We hypothesize that this dynamical transition is a general feature that can be found not only in proteins but also in aggregates that interact with water and that have a flexible structure. In fact this feature has already been found not only in proteins hydration water but also in a colloidal microgel. In the known cases, including the one that we present here, water enhances movements of the surface of these aggregates above a certain temperature. The temperature of this dynamical transition ranges between 260 K and 220 K in all known cases.

How can we derive hydration water dynamics with incoherent neutron scattering and molecular dynamics simulation?

Incoherent neutron scattering (INS) is one of the useful experimental methods for studying protein dynamics at the pico-nanosecond timescale. At this timescale, protein dynamics is highly coupled with hydration, which is observed as protein dynamical transition (PDT). INS is very sensitive to hydrogen atomic dynamics because of the large incoherent scattering cross section of hydrogen atom, and thus, the INS of a hydrated protein provides overall dynamic information about the protein, including hydration water. Separation of hydration water dynamics is essential for understanding hydration-related protein dynamics. H2O/D2O exchange is an effective method in the context of INS experiments for observing the dynamics of protein and hydration water separately. Neutron scattering is directly related to the van Hove space-time correlation function, which can be calculated quantitatively by performing molecular dynamics (MD) simulations. Diffusion and hydrogen bond dynamics of hydration water can be analyzed by performing MD simulation. MD simulation is useful for analyzing the dynamic coupling mechanism in hydration-related protein dynamics from the viewpoint of interpreting INS data because PDT is induced by hydration. In the present work, we demonstrate the methodological advantages of the H2O/D2O exchange technique in INS and the compatibility of INS and MD simulation as tools for studying protein dynamics and hydration water.

Mutual interactions in a ternary protein/bioprotectant/water system

The dynamics of hydration water play a key role in many biological processes. The activity and function of proteins are strongly affected by the presence of water, which interacts primarily by means of hydrogen bonding. These interactions are examined in this work by a comparison of neutron vibrational spectra (Inelastic Neutron Scattering, INS) of dry lysozyme and hydrated lysozyme at h = 0.7 (g of H2O/g of protein) with those of a lysozyme/water mixture at the same hydration value in the presence of the glass-forming bioprotectant trehalose. A difference spectrum, obtained by subtracting the dry lysozyme spectrum from that of the lysozyme/water mixture, yields the hydration water spectrum which is compared to the INS spectra of different kinds of ice in order to determine the changes induced by lysozyme on the hydrogen-bonded network of water. An additional comparison is performed by using a double-difference spectrum obtained by subtracting both the dry lysozyme and the trehalose spectra from the lysozyme/trehalose/water ternary spectrum. The effects of the mutual interactions among the three components, i.e. protein, disaccharide and water, are determined by comparison of the spectra of the dry systems (lysozyme, trehalose) with the difference spectra obtained from subtraction of the dry systems from the binary systems. It is concluded that the interfacial water more strongly affects the intermolecular mode region at low frequencies, whereas the vibrational spectra at high frequencies are more influenced by lysozyme and trehalose.

Structure and slow dynamics of protein hydration water

We report results on the structure, local order and dynamics of water surrounding a lysozyme protein. The local order of water molecules is as much tetrahedral as in bulk water already at close vicinity of the protein but the number of hydrogen bonds depends more on the distance from the protein and gradually recovers bulk value upon moving outer. The dynamics of water seems in general to be more affected than its structure by the presence of the protein. An extremely long-relaxation detected in hydration water appears in the first monolayer around the protein, and the slow down is enhanced at low temperature. The dynamics of water within a layer of thickness 6 Å is sub-diffusive up to about ∼1 ns, above 1 ns we observe a crossover toward a hopping regime over a length-scale larger than that of nearest neighbors molecules. This hopping seems connected to transient trapping of water molecules on some specific protein domains.

Computational discovery of chemically patterned surfaces that effect unique hydration water dynamics

The interactions of water with solid surfaces govern their apparent hydrophobicity/hydrophilicity, influenced at the molecular scale by surface coverage of chemical groups of varied nonpolar/polar character. Recently, it has become clear that the precise patterning of surface groups, and not simply average surface coverage, has a significant impact on the structure and thermodynamics of hydration layer water, and, in turn, on macroscopic interfacial properties. Here we show that patterning also controls the dynamics of hydration water, a behavior frequently thought to be leveraged by biomolecules to influence functional dynamics, but yet to be generalized. To uncover the role of surface heterogeneities, we couple a genetic algorithm to iterative molecular dynamics simulations to design the patterning of surface functional groups, at fixed coverage, to either minimize or maximize proximal water diffusivity. Optimized surface configurations reveal that clustering of hydrophilic groups increases hydration water mobility, while dispersing them decreases it, but only if hydrophilic moieties interact with water through directional, hydrogen-bonding interactions. Remarkably, we find that, across different surfaces, coverages, and patterns, both the chemical potential for inserting a methane-sized hydrophobe near the interface and, in particular, the hydration water orientational entropy serve as strong predictors for hydration water diffusivity, suggesting that these simple thermodynamic quantities encode the way surfaces control water dynamics. These results suggest a deep and intriguing connection between hydration water thermodynamics and dynamics, demonstrating that subnanometer chemical surface patterning is an important design parameter for engineering solid-water interfaces with applications spanning separations to catalysis.

Gradual Crossover from Subdiffusion to Normal Diffusion: A Many-Body Effect in Protein Surface Water

Dynamics of hydration water is essential for the function of biomacromolecules. Previous studies have demonstrated that water molecules exhibit subdiffusion on the surface of biomacromolecules; yet the microscopic mechanism remains vague. Here, by performing neutron scattering, molecular dynamics simulations, and analytic modeling on hydrated perdeuterated protein powders, we found water molecules jump randomly between trapping sites on protein surfaces, whose waiting times obey a broad distribution, resulting in subdiffusion. Moreover, the subdiffusive exponent gradually increases with observation time towards normal diffusion due to a many-body volume-exclusion effect.

How proteins modify water dynamics.

Much of biology happens at the protein-water interface, so all dynamical processes in this region are of fundamental importance. Local structural fluctuations in the hydration layer can be probed by 17O magnetic relaxation dispersion (MRD), which, at high frequencies, measures the integral of a biaxial rotational time correlation function (TCF)-the integral rotational correlation time. Numerous 17O MRD studies have demonstrated that this correlation time, when averaged over the first hydration shell, is longer than in bulk water by a factor 3-5. This rotational perturbation factor (RPF) has been corroborated by molecular dynamics simulations, which can also reveal the underlying molecular mechanisms. Here, we address several outstanding problems in this area by analyzing an extensive set of molecular dynamics data, including four globular proteins and three water models. The vexed issue of polarity versus topography as the primary determinant of hydration water dynamics is resolved by establishing a protein-invariant exponential dependence of the RPF on a simple confinement index. We conclude that the previously observed correlation of the RPF with surface polarity is a secondary effect of the correlation between polarity and confinement. Water rotation interpolates between a perturbed but bulk-like collective mechanism at low confinement and an exchange-mediated orientational randomization (EMOR) mechanism at high confinement. The EMOR process, which accounts for about half of the RPF, was not recognized in previous simulation studies, where only the early part of the TCF was examined. Based on the analysis of the experimentally relevant TCF over its full time course, we compare simulated and measured RPFs, finding a 30% discrepancy attributable to force field imperfections. We also compute the full 17O MRD profile, including the low-frequency dispersion produced by buried water molecules. Computing a local RPF for each hydration shell, we find that the perturbation decays exponentially with a decay "length" of 0.3 shells and that the second and higher shells account for a mere 3% of the total perturbation measured by 17O MRD. The only long-range effect is a weak water alignment in the electric field produced by an electroneutral protein (not screened by counterions), but this effect is negligibly small for 17O MRD. By contrast, we find that the 17O TCF is significantly more sensitive to the important short-range perturbations than the other two TCFs examined here.