Dynamics of water confined in the interdomain region of a multidomain protein

Molecular dynamics simulations are performed to study the dynamics of interfacial water confined in the interdomain region of a two-domain protein, BphC enzyme. The results show that near the protein surface the water diffusion constant is much smaller and the water-water hydrogen bond lifetime is much longer than that in bulk. The diffusion constant and hydrogen bond lifetime can vary by a factor of as much as 2 in going from the region near the hydrophobic domain surface to the bulk. Water molecules in the first solvation shell persist for a much longer time near local concave sites than near convex sites. Also, the water layer survival correlation time shows that on average water molecules near the extended hydrophilic surfaces have longer residence times than those near hydrophobic surfaces. These results indicate that local surface curvature and hydrophobicity have a significant influence on water dynamics.     

Communication: On the locality of hydrogen bond networks at hydrophobic interfaces

The formation of structured hydrogen bond networks in the solvation shells immediate to hydrophobic solutes is crucial for a large number of water mediated processes. A long lasting debate in this context regards the mutual influence of the hydrophobic solute into the bulk water and the role of the hydrogen bond network of the bulk in supporting the solvation structure around a hydrophobic molecule. In this context we present a molecular dynamics study of the solvation of various hydrophobic molecules where the effect of different regions around the solvent can be analyzed by employing an adaptive resolution method, which can systematically separate local and nonlocal factors in the structure of water around a hydrophobic molecule. A number of hydrophobic solutes of different sizes and two different model potential interactions between the water and the solute are investigated.     

Structural and dynamical analysis of the hydration of the Alzheimer's beta-amyloid peptide

An analysis of the water molecules in the first solvation shell obtained from the molecular dynamics simulation of the amyloid beta(10-35)NH2 peptide and the amyloid beta(10-35)NH2E22Q "Dutch" mutant peptide is presented. The structure, energetics, and dynamics of water in the hydration shell have been investigated using a variety of measures, including the hydrogen bond network, the water residence times for all the peptide residues, the diffusion constant, experimentally determined HN amide proton exchange, and the transition probabilities for water to move from one residue to another or into the bulk. The results of the study indicate that: (1) the water molecules at the peptide-solvent interface are organized in an ordered structure similar for the two peptide systems but different from that of the bulk, (2) the peptide structure inhibits diffusion perpendicular to the peptide surface by a factor of 3 to 5 relative to diffusion parallel to the peptide surface, which is comparable to diffusion of bulk water, (3) water in the first solvation shell shows dynamical relaxation on fast (1-2 ps) and slow (10-40 ps) time scales, (4) a novel solvent relaxation master equation is shown to capture the details of the fast relaxation of water in the peptide's first solvation shell, (5) the interaction between the peptide and the solvent is stronger in the wild type than in the E22Q mutant peptide, in agreement with earlier results obtained from computer simulations [Massi, F.; Straub, J. E. Biophys J 2001, 81, 697] correlated with the observed enhanced activity of the E22Q mutant peptide.     

The importance of the shape of the protein-water interface of a kinesin motor domain for dynamics of the surface atoms of the protein

A single kinesin motor domain immersed in water has been investigated using molecular dynamics. It has been found that local properties of water in the solvation shell change along with the nature of the neighboring protein surface. However, a detailed analysis leads to the conclusion that the geometrical features of hydrogen bonds and overall structure of kinesin hydration water are not very different from bulk water. The local values of diffusion coefficients (translational and rotational) of water adjacent to specific patches on the protein surface seem not to be correlated to the orientational ordering of hydration water, but instead they depend on spatial roughness and degree of exposure of the patch to the solvent. Finally, a relationship between the mobility of various surface atoms of the protein and the mean values of the diffusion coefficient of the adjacent water molecules has been observed. The latter finding suggests a close relationship between the dynamics of the inner kinesin movements and the behavior of solvation water which is in turn determined by the topography of the contact surface between the protein and the surrounding water molecules.     

Hydration and dewetting near graphite-CH(3) and graphite-COOH plates

The dynamics of water near the nanoscale hydrophobic (graphite-CH(3)) and hydrophilic (graphite-COOH) plates has been studied in detail with molecular dynamics simulations in this paper. It is shown that these designed surfaces (by growing a layer of methyl or carboxyl groups on top of graphite) can have a significant impact on the neighboring water dynamics, with the hydrophilic carboxyl surface having even more profound effects. The water hydrogen bond lifetime is much longer near both types of surfaces than that in the bulk, while on the other hand the water diffusion constant is much smaller than that in the bulk. The difference in the diffusion constant can be as large as a factor of 8 and the difference in the hydrogen bond lifetime can be as large as a factor of 2, depending on the distance from the surface. Furthermore, the water molecules in the first solvation shell of surface atoms show a strong bias in hydroxyl group orientation near the surface, confirming some of the previous findings. Finally, the possible water dewetting transition between two graphite-CH(3) plates and the effect of the strength of the solute-solvent attractions on the water drying transition are investigated. The relationship among the dewetting transition critical distance, van der Waals potential well depth, and water contact angle on the graphite-CH(3) surface is also analyzed on the basis of a simple macroscopic theory, which can be used to predict the dewetting transition critical distance.     

Solvation structure of hydroxyl radical by Car-Parrinello molecular dynamics

Car-Parrinello molecular dynamics simulations of a hydroxyl radical in liquid water have been performed. Structural and dynamical properties of the solvated structure have been studied in details. The partial atom-atom radial distribution functions for the hydrated hydroxyl do not show drastic differences with the radial distribution functions for liquid water. The OH is found to be a more active hydrogen bond donor and acceptor than the water molecule, but the accepted hydrogen bonds are much weaker than for the hydroxide OH- ion. The first solvation shell of the OH is less structured than the water's one and contains a considerable fraction of water molecules that are not hydrogen bonded to the hydroxyl. Part of them are found to come closer to the solvated radical than the hydrogen bonded molecules do. The lifetime of the hydrogen bonds accepted by the hydroxyl is found to be shorter than the hydrogen bond lifetime in water. A hydrogen transfer between a water molecule and the OH radical has been observed, though it is a much rarer event than a proton transfer between water and an OH- ion. The velocity autocorrelation power spectrum of the hydroxyl hydrogen shows the properties both of the OH radical in clusters and of the OH- ion in liquid.     

Structural properties of water: comparison of the SPC, SPCE, TIP4P, and TIP5P models of water

Molecular-dynamics simulations were carried out for the SPC, SPCE, TIP4P, and TIP5P models of water at 298 K. From these results we determine the following quantities: the absolute entropy using the two-particle approximation, the mean lifetime of the hydrogen bond, the mean number of hydrogen bonds per molecule, and the mean energy of the hydrogen bond. From the entropy calculations we find that nearly all contributions to the total entropy originates from the orientation effects. Moreover, we determine the contributions to the total entropy which originate from the first, second, and higher solvation shells. It is interesting that the limits between solvation shells are clearly visible. The first solvation shell (0.22 < r < 0.36 nm) contributes approximately 43 J mol K to the total entropy; the second solvation shell (0.36 < r < 0.60 nm) contributes approximately 12 J mol K, while contributions from the third and other solvation shells are very small, approximately 2 J mol K in summary. This indicates that water molecules are strongly ordered up to 0.55-0.6 nm around the central water molecule, and beyond this limit the ordering diminishes. The results of calculations (entropy and hydrogen bonds) are compared with the experimental data for the choosing of the best water model. We find that the SPC and TIP4P models reproduce the best experimental values, and we recommend these models for computer simulations of the aqueous solution of biomolecules.     

Potential of mean force of hydrophobic association: dependence on solute size

The potentials of mean force (PMFs) were determined for systems involving formation of nonpolar dimers composed of methane, ethane, propane, isobutane, and neopentane, respectively, in water, using the TIP3P water model, and in vacuo. A series of umbrella-sampling molecular dynamics simulations with the AMBER force field was carried out for each pair in either water or in vacuo. The PMFs were calculated by using the weighted histogram analysis method (WHAM). The shape of the PMFs for dimers of all five nonpolar molecules is characteristic of hydrophobic interactions with contact and solvent-separated minima and desolvation maxima. The positions of all these minima and maxima change with the size of the nonpolar molecule, that is, for larger molecules they shift toward larger distances. The PMF of the neopentane dimer is similar to those of other small nonpolar molecules studied in this work, and hence the neopentane dimer is too small to be treated as a nanoscale hydrophobic object. The solvent contribution to the PMF was also computed by subtracting the PMF determined in vacuo from the PMF in explicit solvent. The molecular surface area model correctly describes the solvent contribution to the PMF together with the changes of the height and positions of the desolvation barrier for all dimers investigated. The water molecules in the first solvation sphere of the dimer are more ordered compared to bulk water, with their dipole moments pointing away from the surface of the dimer. The average number of hydrogen bonds per water molecule in this first hydration shell is smaller compared to that in bulk water, which can be explained by coordination of water molecules to the hydrocarbon surface. In the second hydration shell, the average number of hydrogen bonds is greater compared to bulk water, which can be explained by increased ordering of water from the first hydration shell; the net effect is more efficient hydrogen bonding between the water molecules in the first and second hydration shells.     

X-ray absorption spectroscopy study of the hydrogen bond network in the bulk water of aqueous solutions

We utilized X-ray absorption spectroscopy (XAS) and X-ray Raman scattering (XRS) in order to study the ion solvation effect on the bulk hydrogen bonding structure of water. The fine structures in the X-ray absorption spectra are sensitive to the local environment of the probed water molecule related to the hydrogen bond length and angles. By varying the concentration of ions, we can distinguish between contributions from water in the bulk and in the first solvation sphere. We show that the hydrogen bond network in bulk water, in terms of forming and breaking hydrogen bonds as detected by XAS/XRS, remains unchanged, and only the water molecules in the close vicinity to the ions are affected.     

The effect of pressure on the hydration structure around hydrophobic solute: a molecular dynamics simulation study

Molecular dynamics simulations are performed to study the effects of pressure on the hydrophobic interactions between neopentane molecules immersed in water. Simulations are carried out for five different pressure values ranging from 1 atm to 8000 atm. From potential of mean force calculations, we find that with enhancement of pressure, there is decrease in the well depth of contact minimum (CM) and the relative stability of solvent separated minimum over CM increases. Lower clustering of neopentane at high pressure is also observed in association constant and cluster-structure analysis. Selected site-site radial distribution functions suggest efficient packing of water molecules around neopentane molecules at elevated pressure. The orientational profile calculations of water molecules show that the orientation of water molecules in the vicinity of solute molecule is anisotropic and this distribution becomes flatter as we move away from the solute. Increasing pressure slightly changes the water distribution. Our hydrogen bond properties and dynamics calculations reveal pressure-induced formation of more and more number of water molecules with five and four hydrogen bond at the expense of breaking of two and three hydrogen bonded water molecules. We also find lowering of water-water continuous hydrogen bond lifetime on application of pressure. Implication of these results for relative dispersion of hydrophobic molecules at high pressure are discussed.     

Ions in water: the microscopic structure of concentrated NaOH solutions

A neutron diffraction experiment with isotopic H/D substitution on four concentrated NaOH/H(2)O solutions is presented. The full set of partial structure factors is extracted, by combining the diffraction data with a Monte Carlo simulation. These allow to investigate both the changes of the water structure in the presence of ions and their solvation shells. It is found that the interaction with the solute affects the tetrahedral network of hydrogen bonded water molecules in a manner similar to the application of high pressure to pure water. The solvation shell of the OH(-) ions has an almost concentration independent structure, although with concentration dependent coordination numbers. The hydrogen site coordinates a water molecule through a weak bond, while the oxygen site forms strong hydrogen bonds with a number of molecules that is on the average very close to four at the higher water concentrations and decreases to about three at the lowest one. The competition between hydrogen bond interaction and Coulomb forces in determining the orientation of water molecules within the cation solvation shell is visible in the behavior of the g(NaHw)(r) function     

Hydrogen bond breaking mechanism and water reorientational dynamics in the hydration layer of lysozyme

The mechanism and the rate of hydrogen bond-breaking in the hydration layer surrounding an aqueous protein are important ingredients required to understand the various aspects of protein dynamics, its function, and stability. Here, we use computer simulation and a time correlation function technique to understand these aspects in the hydration layer of lysozyme. Water molecules in the layer are found to exhibit three distinct bond-breaking mechanisms. A large angle orientational jump of the donor water molecule is common among all of them. In the most common ( approximately 80%) bond-breaking event in the layer, the new acceptor water molecule comes from the first coordination shell (initially within 3.5 A of the donor), and the old acceptor water molecule remains within the first coordination shell, even after the bond-breaking. This is in contrast to that in bulk water, in which both of the acceptor molecules involve the second coordination shell. Additionally, the motion of the incoming and the outgoing acceptor molecules involved is not diffusive in the hydration layer, in contrast to their observed diffusive motion in the bulk. The difference in rotational dynamics between the bulk and the hydration layer water molecules is clearly manifested in the calculated time-dependent angular van Hove self-correlation function ( G(theta, t)) which has a pronounced two-peak structure in the layer, and this can be traced to the constrained translational motion in the layer. The longevity of the surrounding hydrogen bond network is found to be significantly enhanced near a hydrophilic residue.     

Combined use of Overhauser spectroscopy and NMR diffusion experiments for mapping the hydration structure of nucleosides: structure and dynamics of uridine in water

Complementary results from 13C intermolecular nuclear Overhauser effects (NOE), 1H-13C heteronuclear Overhauser spectroscopy (HOSEY) and 1H-NMR diffusion measurements were used for probing the structure of the first solvation shell of uridine in water. It is demonstrated that a cyclic dihydrate is formed. The two water molecules produce two hydrogen bonds with the two oxygen atoms from the pyrimidine ring and accept only one hydrogen bond from the amide proton. The dihydrate has only a short lifetime as compared with the rotational correlation time of the free nucleoside. The chemical exchange constant of the amide proton with water is then estimated by diffusion experiments. The results are consistent with previous data obtained for uracil in water and provide interesting information about water accessibility in nucleic acid bases.     

Water's hydrogen bonds in the hydrophobic effect: a simple model

We propose a simple analytical model to account for water's hydrogen bonds in the hydrophobic effect. It is based on computing a mean-field partition function for a water molecule in the first solvation shell around a solute molecule. The model treats the orientational restrictions from hydrogen bonding, and utilizes quantities that can be obtained from bulk water simulations. We illustrate the principles in a 2-dimensional Mercedes-Benz-like model. Our model gives good predictions for the heat capacity of hydrophobic solvation, reproduces the solvation energies and entropies at different temperatures with only one fitting parameter, and accounts for the solute size dependence of the hydrophobic effect. Our model supports the view that water's hydrogen bonding propensity determines the temperature dependence of the hydrophobic effect. It explains the puzzling experimental observation that dissolving a nonpolar solute in hot water has positive entropy.     

Hydrogen bond dynamics and water structure in glucose-water solutions by depolarized Rayleigh scattering and low-frequency Raman spectroscopy

The effect of glucose on the relaxation process of water at picosecond time scales has been investigated by depolarized Rayleigh scattering (DRS) experiments. The process is assigned to the fast hydrogen bonding dynamics of the water network. In DRS spectra this contribution can be safely separated from the slower relaxation process due to the sugar. The detected relaxation time is studied at different glucose concentrations and modeled considering bulk and hydrating water contributions. As a result, it is found that in diluted conditions the hydrogen bond lifetime of proximal water molecules becomes about three times slower than that of the bulk. The effect of the sugar on the hydrogen bond water structure is investigated by analyzing the low-frequency Raman (LFR) spectrum sensitive to intermolecular modes. The addition of glucose strongly reduces the intensity of the band at 170 cm(-1) assigned to a collective stretching mode of water molecules arranged in cooperative tetrahedral domains. These findings indicate that proximal water molecules partially lose the tetrahedral ordering typical of the bulk leading to the formation of high density environments around the sugar. Thus the glucose imposes a new local order among water molecules localized in its hydration shell in which the hydrogen bond breaking dynamics is sensitively retarded. This work provides new experimental evidences that support recent molecular dynamics simulation and thermodynamics results.     

A first principles molecular dynamics study of lithium atom solvation in binary liquid mixture of water and ammonia: structural, electronic, and dynamical properties

The preferential solvation of solutes in mixed solvent systems is an interesting phenomenon that plays important roles in solubility and kinetics. In the present study, solvation of a lithium atom in aqueous ammonia solution has been investigated from first principles molecular dynamics simulations. Solvation of alkali metal atoms, like lithium, in aqueous and ammonia media is particularly interesting because the alkali metal atoms release their valence electrons in these media so as to produce solvated electrons and metal counterions. In the present work, first principles simulations are performed employing the Car-Parrinello molecular dynamics method. Spontaneous ionization of the Li atom is found to occur in the mixed solvent system. From the radial distribution functions, it is found that the Li(+) ion is preferentially solvated by water and the coordination number is mostly four in its first solvation shell and exchange of water molecules between the first and second solvation shells is essentially negligible in the time scale of our simulations. The Li(+) ion and the unbound electron are well separated and screened by the polar solvent molecules. Also the unbound electron is primarily captured by the hydrogens of water molecules. The diffusion rates of Li(+) ion and water molecules in its first solvation shell are found to be rather slow. In the bulk phase, the diffusion of water is found to be slower than that of ammonia molecules because of strong ammonia-water hydrogen bonds that participate in solvating ammonia molecules in the mixture. The ratio of first and second rank orientational correlation functions deviate from 3, which suggests a deviation from the ideal Debye-type orientational diffusion. It is found that the hydrogen bond lifetimes of ammonia-ammonia pairs is very short. However, ammonia-water H-bonds are found to be quite strong when ammonia acts as an acceptor and these hydrogen bonds are found to live longer than even water-water hydrogen bonds.     

Probing the transition from hydrophilic to hydrophobic solvation with atomic scale resolution

Picosecond and femtosecond X-ray absorption spectroscopy is used to probe the changes of the solvent shell structure upon electron abstraction of aqueous iodide using an ultrashort laser pulse. The transient L(1,3) edge EXAFS at 50 ps time delay points to the formation of an expanded water cavity around the iodine atom, in good agreement with classical and quantum mechanical/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. These also show that while the hydrogen atoms pointed toward iodide, they predominantly point toward the bulk solvent in the case of iodine, suggesting a hydrophobic behavior. This is further confirmed by quantum chemical (QC) calculations of I(-)/I(0)(H(2)O)(n=1-4) clusters. The L(1) edge sub-picosecond spectra point to the existence of a transient species that is not present at 50 ps. The QC calculations and the QM/MM MD simulations identify this transient species as an I(0)(OH(2)) complex inside the cavity. The simulations show that upon electron abstraction most of the water molecules move away from iodine, while one comes closer to form the complex that lives for 3-4 ps. This time is governed by the reorganization of the main solvation shell, basically the time it takes for the water molecules to reform an H-bond network. Only then is the interaction with the solvation shell strong enough to pull the water molecule of the complex toward the bulk solvent. Overall, much of the behavior at early times is determined by the reorientational dynamics of water molecules and the formation of a complete network of hydrogen bonded molecules in the first solvation shell.     

Hydrophilicity and Microsolvation of an Organic Molecule Resolved on the Sub‐molecular Level by Scanning Tunneling Microscopy

Low‐temperature scanning tunneling microscopy was used to follow the formation of a solvation shell around an adsorbed functionalized azo dye from the attachment of the first water molecule to a fully solvated molecule. Specific functional groups bind initially one water molecule each, which act as anchor points for additional water molecules. Further water attachment occurs in areas close to these functional groups even when the functional groups themselves are already saturated. In contrast, water molecules surround the hydrophobic parts of the molecule only when the two‐dimensional solvation shell closes around them. This study thus traces hydrophilic and hydrophobic properties of an organic molecule down to a sub‐molecular length scale.     

Strength of hydrogen bonds of water depends on local environment

In-depth knowledge of water-water potential is important for devising and evaluating simple water models if they are to accurately describe water properties and reflect various solvation phenomena. Water-water potential depends upon inter-molecular distance, relative orientation of water molecules, and also local environment. When placed at a favorable distance in a favorable orientation, water molecules exhibit a particularly strong attractive interaction called hydrogen bond. Although hydrogen bond is very important for its effects on the elements of life, industrial applications, and bulk water properties, there is no scientific consensus on its true nature and origin. Using quantum-mechanical methods, hydrogen bond strength was calculated in different local environments. A simple empirical linear relationship was discovered between maximum hydrogen bond strength and the number of water molecules in the local environment. The local environment effect was shown to be considerable even on the second coordination shell. Additionally, a negative linear correlation was found between maximum hydrogen bond strength and the distance, at which it was observed. These results provide novel insights into the nature of hydrogen bonding.     

Hydrophobic hydration in an orientational lattice model

To shed light on the microscopic mechanism of hydrophobic hydration, we study a simplified lattice model for water solutions in which the orientational nature of hydrogen bonding as well as the degeneracy related to proton distribution are taken into account. Miscibility properties of the model are looked at for both polar (hydrogen bonding) and nonpolar (non-hydrogen bonding) solutes. A quasichemical solution for the pure system is reviewed and extended to include the different kinds of solute. A Monte Carlo study of our model yields a novel feature for the local structure of the hydration layer: energy correlation relaxation times for solvation water are larger than the corresponding relaxation times for bulk water. This result suggests the presence of ordering of water particles in the first hydration shell. A nonassociating model solvent, represented by a lattice gas, presents opposite behavior, indicating that this effect is a result of the directionality of the interaction. In presence of polar solutes, we find an ordered mixed pseudophase at low temperatures, indicating the possibility of closed loops of immiscibility.