Structure Of Surrounding Water Research Articles

Leveraging a Separation of States Method for Relative Binding Free Energy Calculations in Systems with Trapped Waters.

Methods for calculating the relative binding free energy (RBFE) between ligands to a target protein are gaining importance in the structure-based drug discovery domain, especially as methodological advances and automation improve accuracy and ease of use. In an RBFE calculation, the difference between the binding affinities of two ligands to a protein is calculated by transforming one ligand into another, in the protein-ligand complex, and in solvent. Alchemical binding free energy calculations are often used for such ligand transformations. Such calculations are not without challenges, however; for example, it can be challenging to handle interfacial waters when these play a crucial role in mediating protein-ligand binding. In some cases, the exchange of the interfacial waters with solvent water might be very infrequent in the course of typical molecular simulations, and such interfacial waters can be considered trapped on the simulation time scale. In these cases, RBFE calculation between two ligands, where one ligand binds with a trapped water while the other ligand displaces it, can result in inaccuracies if the surrounding water structure is not sampled adequately for both ligands. So far, a popular choice for treating the trapped waters in RBFE calculations is to combine free energy calculations with enhanced sampling methods that insert/delete waters in the binding site. Despite recent developments in the enhanced sampling methods, they can result in hysteresis in the RBFE estimate, depending on whether the simulations were started with or without the trapped waters. In this study, we introduce an alternative method, separation of states, to calculate the RBFE between ligand pairs where the ligands bind to the protein with different numbers/positions of trapped waters. The separation of states approach treats the sampling of the trapped waters separately from the free energy calculation of the ligand transformation. In our method, a trapped water in protein's binding site is decoupled from the system first, and the cavity created by its decoupling is stabilized. We then grow a larger ligand into this cavity- a ligand that is known to displace the trapped water. In this study, we show that our method results in precise and accurate estimates of RBFEs for ligand pairs involving the rearrangement of trapped water via RBFE calculations for five such ligand pairs. We have optimized our simulation protocol to be suited for large distributed computational resources and have automated our RBFE calculation workflow.

The Microstructural Investigation and the Temperature-Changing Separation of Brine with a High Mg/Li Ratio

The difficult separation of magnesium–lithium has always been a problem that impedes the comprehensive utilization of salt lake brine resources. In this paper, a method for the separation of magnesium and lithium based on the crystallization of magnesium sulfate at high-temperature supersaturation and a low viscosity was investigated. The microstructure of soluble solutions was analyzed, and the results showed that, in a single-salt solution, controlling the temperature can change the contact ion pair structure of MgSO4 solution, and the arrangement of SO42− and H2O in the second hydration layer changes. In the Li2SO4 solution, the hydrogen bonds between SO42− and H2O break, and the surrounding water structure changes, breaking the similarity of the microstructure of magnesium–lithium and enhancing the separation effect. In a multi-ion system, the change in water structure in the solution decreases with the increase in Cl− concentration. Controlling the temperature of salt lake brine with different magnesium–lithium mass ratios, it was found that the magnesium–lithium mass ratio in the brine could be reduced by one-third; when the magnesium–lithium mass ratio was 10:1~160:1, the loss of lithium could be controlled within 5%, but when the magnesium–lithium mass ratio was 5:1, the loss of lithium was 25.06%. The main reason for lithium loss is that Li2SO4 in the liquid phase enters the solid phase as a cluster and is entrapped during the MgSO4 crystallization process. The entire experiment shows that controlling the temperature process is more suitable for salt lake brine with a high magnesium–lithium ratio.

Hydrophobic Effect on Gas Hydrate Formation in the Presence of Additives

Additives such as surfactants, polymers, salts, and hydrophobic particles are well-known (and used) to influence gas hydrate formation (GHF). This paper reviews and discusses the mechanisms of their effects. The effects of additives on GHF appear to vary greatly from one additive to another. Even a given additive can change from a promoter to an inhibitor and vice versa when the working conditions are changed. The available literature cannot explain the diverse effects of additives. We argue that the hydrophobic effect plays a critical role in gas hydrate formation. A dissolved hydrophobe organizes the surrounding water into a clathrate-like structure and thereby promotes hydrate formation. A hydrophile, however, disrupts the surrounding water structure and inhibits hydrate formation. Moreover, cooperative hydrophobic interactions create an increased gas concentration around a hydrophobe, which also favors the hydrate formation. In contrast, a hydrophile competes with the gas for water and thereby hinders...

Low-Frequency Modes of Aqueous Alkali Halide Solutions: Glimpsing the Hydrogen Bonding Vibration

The solvation of ions in aqueous media is a fundamental process in biology and chemistry. Here, we report direct time-domain observations of the hydrogen bond vibrational mode formed between a halide ion (chloride, bromide, or iodide) and the surrounding water molecules. The frequency of the hydrogen bond mode is sensitive to both the atomic weight and the concentration of the ion. The peak frequencies fall in the 125 to 175 wave-number range, a spectral region accessed through time-domain polarization-resolved coherent Raman scattering using a diffractive optic method. The polarized Raman response observed is discussed in terms of the structure of the anion's solvation shell and modeled through calculations on water chloride clusters.

How hydrophobic buckminsterfullerene affects surrounding water structure.

The hydrophobic hydration of fullerenes in water is of significant interest as the most common Buckminsterfullerene (C60) is a mesoscale sphere; C60 also has potential in pharmaceutical and nanomaterial applications. We use an all-atom molecular dynamics simulation lasting hundreds of nanoseconds to determine the behavior of a single molecule of C60 in a periodic box of water, and compare this to methane. A C60 molecule does not induce drying at the surface; however, unlike a hard sphere methane, a hard sphere C60 solute does. This is due to a larger number of attractive Lennard-Jones interactions between the carbon atom centers in C60 and the surrounding waters. In these simulations, water is not uniformly arranged but rather adopts a range of orientations in the first hydration shell despite the spherical symmetry of both solutes. There is a clear effect of solute size on the orientation of the first hydration shell waters. There is a large increase in hydrogen-bonding contacts between waters in the C60 first hydration shell. There is also a disruption of hydrogen bonds between waters in the first and second hydration shells. Water molecules in the first hydration shell preferentially create triangular structures that minimize the net water dipole near the surface near both the methane and C60 surface, reducing the total energy of the system. Additionally, in the first and second hydration shells, the water dipoles are ordered to a distance of 8 A from the solute surface. We conclude that, with a diameter of approximately 1 nm, C60 behaves as a large hydrophobic solute.

Trans-Sodium Crocetinate and Diffusion Enhancement

trans-Sodium crocetinate (TSC) increases the diffusion coefficient of glucose through water by about 25-30%. This is the same percentage increase that TSC causes in the diffusivity of oxygen through water. TSC is also found to induce order in the surrounding water structure through increased hydrogen bonding of the water molecules, and molecular simulations suggest that the increase in diffusivity occurs only in these ordered regions.

Carbohydrate Intramolecular Hydrogen Bonding Cooperativity and Its Effect on Water Structure

Molecular dynamics (MD) simulations combined with water-water H-bond angle analysis and calculation of solvent accessible surface area and approximate free energy of solvation were used to determine the influence of hydroxyl orientation on solute hydration and surrounding water structure for a group of chemically identical solutes-the aldohexopyranose sugars. Intramolecular hydrogen bond cooperativity was closely associated with changes in water structure surrounding the aldohexopyranose stereoisomers. The OH-4 group played a pivotal role in hydration as it was able to participate in a number of hydrogen bond networks utilizing the OH-6 group. Networks that terminated within the molecule (OH-4 --> OH-6 --> O-5) had relatively more nonpolar-like hydration than those that ended in a free hydroxyl group (OH-6 --> OH-4 --> OH-3). The OH-2 group modulated the strength of OH-4 networks through syndiaxial OH-2/4 intramolecular hydrogen bonding, which stabilized and induced directionality in the network. Other syndiaxial interactions, such as the one between OH-1 and OH-3, only indirectly affected water structure. Water structure surrounding hydrogen bond networks is discussed in terms of water-water hydrogen bond populations. The impact of syndiaxial versus vicinal hydrogen bonds is also reviewed. The results suggest that biological events such as protein-carbohydrate recognition and cryoprotection by carbohydrates may be driven by intramolecular hydrogen bond cooperativity.

Ab initio molecular dynamics simulations of β- d-glucose and β- d-xylose degradation mechanisms in acidic aqueous solution

Ab initio molecular dynamics simulations were employed to investigate, with explicit solvent water molecules, β- d-glucose and β- d-xylose degradation mechanisms in acidic media. The rate-limiting step in sugar degradation was found to be protonation of the hydroxyl groups on the sugar ring. We found that the structure of water molecules plays a significant role in the acidic sugar degradation pathways. Firstly, a water molecule competes with the hydroxyl group on the sugar ring for protons. Secondly, water forms hydrogen bonds with the hydroxyl groups on the sugar rings, thus weakening the C–C and C–O bonds (each to a different degree). Note that the reaction pathways could be altered due to the change of relative stability of the C–C and C–O bonds. Thirdly, water molecules that are hydrogen-bonded to sugar hydroxyls could easily extract a proton from the reaction intermediate, terminating the reaction. Indeed, the sugar degradation pathway is complex due to multiple protonation probabilities and the surrounding water structure. Our experimental data support multiple sugar acidic degradation pathways.

Dependence of ion hydration on the sign of the ion’s charge

The solvation of simple ions in water is studied using molecular dynamics simulations with a polarizable force field. Previous simulations using this potential demonstrated that anions are more favorably solvated in water than cations. The present work is an attempt to explain this result by examining the effects of ions on the surrounding water structure, with particular focus on the first solvation shell and its interactions with the surrounding water. We conclude that while the first solvation shell surrounding cations is frustrated by competition between ion-water and water-water interactions, solvation of anions is compatible with good water-water interactions.

Oligosaccharides as Model Systems for Understanding Water−Biopolymer Interaction: Hydrated Dynamics of a Hyaluronan Decamer

Hyaluronan is a mammalian extracellular maxtrix polysaccharide with unusual physiochemical properties. In this study, a five-nanosecond simulation of a hyaluronan decasaccharide in aqueous solution was compared with previous experimental data and hence used as a model system for studying carbohydrate−water interactions. The predicted average conformation is in agreement with X-ray fiber diffraction and hydrodynamic predictions, but the calculated persistence length is larger than that inferred from experiments, as is expected from the lack of counterions in this simulation. Intramolecular hydrogen bonds were observed in the simulation across all sugar linkages, but they are predicted to be in exchange with water and with themselves. Some 80 distinct intramolecular hydrogen-bond interactions were documented over a period of 1 nanosecond in this short length of polymer. Therefore, it is predicted that individual intramolecular hydrogen bonds will be difficult to observe directly by nuclear magnetic resonance spectroscopy or other experimental techniques. However, the simulation also predicts that this exchange is atypical at the terminal linkages of the polymer. Such end-effects have been proposed from interpretation of nuclear magnetic resonance spectroscopy and circular dichroism measurements. In summary, water interaction resulted in a molecular end-to-end distance that was consistently close to the maximum. However, there were strong but ephemeral fluctuations on the subnanosecond time scale away from the most extended state, involving large rearrangements of the surrounding water structure. This dynamic model for hyaluronan extends the current static microscopic view, while also being consistent with large-scale stiffened random-coil models. Therefore, it is proposed that these microscopic properties, emergent from water interaction, are responsible for the macroscopic physicochemical properties of this molecule. These results motivate the design of novel prediction-testing experiments, which can throw new light on water−biopolymer interactions.

Solution properties of ethanol in water

The packing propensity of ethanol in aqueous solution is very unusual, yet ethanol finds extensive use both in the food and the pharmaceutical industry. An analysis of the solution properties of increasing concentrations of ethanol in water at 20° and 37°C reveals valuable information about its packing characteristics. Apparent molar and specific volumes provide information about the interaction of ethanol with surrounding water structure. Isentropic apparent molar and specific compressibilities indicate the extent to which the hydration layer around the ethanol molecules can be compressed. Compressibility hydration numbers show the number of water molecules that are displaced by the introduction of the ethanol to water. The enhanced packing efficiency of ethanol in water at low concentrations, is affected by the formation of cage-like structures around the hydrophobic end of the molecule. At high concentrations, however, linear chains or rings of ethanol molecules are formed which change its mode of packing within the three-dimensional structure of water. These effects may be used to help explain the mechanism of action of ethanol in food, pharmaceutical and other applications.

The importance of the hydrophobic components of the binding energies in the interaction of omega-amino acid ligands with isolated kringle polypeptide domains of human plasminogen.

Three of the five kringle domains of human plasminogen (HPg), viz the first, fourth and fifth, exhibit significantly strong binding to omega-amino acids, such as epsilon-aminocaproic acid (EACA) and transaminomethylcyclohexane-1-carboxylic acid (AMCHA). In all cases, ligand stabilization is due to ion dipole attractions of its charged groups with polypeptide side chains, as well as hydrophobic clustering of the ligand methylene groups with appropriate hydrophobic residues within the kringle domain. In order to estimate the significance of the hydrophobic components of ligand stabilization, we have sought a more detailed description of these binding interactions. The standard thermodynamic binding parameters, delta G degrees, delta H degrees and delta S degrees, for association of EACA and AMCHA with isolated recombinant kringle regions of HPg have been determined at several temperatures to evaluate the changes in standard heat capacities (delta C degrees p) accompanying these interactions. In each case, the delta C degrees p values of binding were negative and in the range -36 to -91 cal mol -1 K -1, reflective of the importance of the hydrophobic components of the binding process and their probable effects on surrounding water structure.

Hydration of oligosaccharides: Anomalous hydration ability of trehalose

The dissacharide trehalose extensively exists in anhydrobiotic organism and is considered to play an important role in preserving the integrity of biomembrane. However, the preserving mechanism remains unclear. In this report, we examine the hydration abilities of trehalose and several oligosaccharides composed of α- d-glucopyranosyl residues. The unfrozen water fraction per molecule was determined from differential scanning calorimetry measurements of their aqueous solutions. Further, the NMR relaxation time of the natural abundance 17O of water is measured for several saccharide solutions. These results indicate that trehalose has the highest hydration ability among the saccharides studied. In other words, trehalose can effectively lower the mobility of water molecules hydrogen-bonded with saccharides. It is thus reasonable that, among the disaccharides studied, trehalose exhibits the maximum stabilizing effect on the bilayer structure of lipid whose acyl chains are bonded with each other by the apolar interaction, because the apolar interaction is strengthened with the stabilization of the surrounding water structure.

Molecular Dynamics Study of an Aqueous LiF Solution

Abstract The structure and properties of a 1.791 molal aqueous LiF solution is investigated by performing molecular dynamics simulations using a water model with both bond flexibility and instantaneously responsive polarization. On average, each cation is in close contact with about one anion. This causes a strong overlap of the hydration shells and an almost complete breakdown of the surrounding water structure. While the lone pairs of the hydration waters in the first Li+ shell occupy preferentially tetrahedral positions, the orientational distribution of the solvent molecules around F--is quite uniform. By comparing various autocorrelation functions of water molecules in the solution and in the pure liquid, the influence of solvated ions on the translational, rotational and vibrational motions of hydration water can be studied

Crystal structure of subtilisin BPN′ variants containing disulfide bonds and cavities: Concerted structural rearrangements induced by mutagenesis

The X-ray structures of four genetically engineered disulfide variants of subtilisin have been analyzed to determine the energetic and structural constraints involved in inserting disulfide bonds into proteins. Each of the engineered disulfides exhibited atypical sets of dihedral angles compared with known structures of natural disulfide bridges in proteins and affected its local structural environment to a different extent. The disulfides located in buried regions, Cys26-Cys232 and Cys29-Cys119, induced larger changes than did Cys24-Cys87 and Cys22-Cys87, which are located on the surface of the molecule. An analysis of the concerted changes in secondary structure units such as alpha-helices and beta-sheets indicated systematic long-range effects. The observed changes in the mutants were largely distributed asymmetrically around the inserted disulfides, reflecting different degrees of inherent flexibility of neighboring secondary structure types. The disulfide substitution in each variant molecule created some invaginations or cavities, causing a reorganization of the surrounding water structure. These changes are described, as well as the changes in side chain positions of groups that border the cavities.

Thermodynamic properties of aqueous solutions of hydrophobic solutes

The existence of hydrophobic hydration is well established. Examples are found for aqueous systems containing purely nonpolar groups (e.g., rare gases, alkanes and perflouroalkanes), poly-functional solutes (e.g., alcohols, ethers and ketones), and ionic solutes (e.g., tetraalkylammonium and azoniaspiroalkane ions). Influence of solute shape on the surrounding water structure is subtle but of particular interest. The ‘structure promotion’ effect in dilute aqueous solutions of hydrophobic groups is now firmly established, but the quantitative details are still incompletely understood. Recent advance in understanding the nature of hydrophobic hydration is made by Frank who pointed out that the hydrophobic hydration is not the cause of the low solubility of nonpolar gases in water. Hydrophobic bonding, which denotes the tendency of non polar groups in water to attract each other, is concentration dependent and not well characterized quantitatively. Several types of examples will be given in which the details of such interactions have been worked out.

THE AQUEOUS SOLUTION BEHAVIOR OF LARGE UNIVALENT IONS. A NEW TYPE OF ION-PAIRING1a

For large, unhydrated, univalent ions, a tightening of the surrounding water structure is a dominant feature of their aqueous solution behavior. As represented by their activity and osmotic coefficients, this corresponds to a rise in the coefficients above the Debye-Huckel limiting law, and the increase is larger, the larger the ion, but if both the cation and anion are such large hydrophobic ions, the hydrogenbonded water structure forces them together to maximize the water-water interactions and to minimize the disturbance to itself. This water structure-enforced ion-pairing is every different from the more usual electrostatic, or Bjerrum, type of ion-pairing, occurring oniy in water, or other highly hydrogen-bonded solvents, and being greater, the larger the ions and the smaller their charges. Some chemical results of this type of ion-pairing are discussed. (auth)