Structure and dynamics of methanol in water: a quantum mechanical charge field molecular dynamics study

An ab initio quantum mechanical charge field molecular dynamics simulation was carried out for one methanol molecule in water to analyze the structure and dynamics of hydrophobic and hydrophilic groups. It is found that water molecules around the methyl group form a cage-like structure whereas the hydroxyl group acts as both hydrogen bond donor and acceptor, thus forming several hydrogen bonds with water molecules. The dynamic analyses correlate well with the structural data, evaluated by means of radial distribution functions, angular distribution functions, and coordination number distributions. The overall ligand mean residence time, τ identifies the methanol molecule as structure maker. The relative dynamics data of hydrogen bonds between hydroxyl of methanol and water molecules prove the existence of both strong and weak hydrogen bonds. The results obtained from the simulation are in excellent agreement with the experimental results for dilute solution of CH(3)OH in water. The overall hydration shell of methanol consists in average of 18 water molecules out of which three are hydrogen bonded.     

Local heterogeneous dynamics of water around lysozyme: a computer simulation study

Water present near the surface of a protein exhibits dynamic properties different from that of water in the pure bulk state. In this work, we have carried out atomistic molecular dynamics simulation of an aqueous solution of hen egg-white lysozyme. Attempts have been made to explore the correlation between the local heterogeneous mobility of water around the protein segments and the rigidity of the hydration layers with the microscopic dynamics of hydrogen bonds formed by water molecules with the protein residues. The kinetics of breaking and reformation of hydrogen bonds involving the surface water molecules have been calculated. It is found that the reformations of broken hydrogen bonds are more frequent for the hydration layers of those segments of the protein that are more rigid. The calculation of the low-frequency vibrational modes of hydration layer water molecules reveals that the protein influences the transverse and longitudinal degrees of freedom of water around it in a differential manner. These findings can be verified by appropriate experimental studies.     

A new angle on heat capacity changes in hydrophobic solvation

The differential solubility of polar and apolar groups in water is important for the self-assembly of globular proteins, lipid membranes, nucleic acids, and other specific biological structures through hydrophobic and hydrophilic effects. The increase in water's heat capacity upon hydration of apolar compounds is one signature of the hydrophobic effect and differentiates it from the hydration of polar compounds, which cause a decrease in heat capacity. Water structuring around apolar and polar groups is an important factor in their differential solubility and heat capacity effects. Here, it is shown that joint radial/angular distribution functions of water obtained from simulations reveal quite different hydration structures around polar and apolar groups: polar and apolar groups have a deficit or excess, respectively, of "low angle hydrogen bonds". Low angle hydrogen bonds have a larger energy fluctuation than high angle bonds, and analysis of these differences provides a physical reason for the opposite changes in heat capacity and new insight into water structure around solutes and the hydrophobic effect.     

Can the anomalous aqueous solubility of beta-cyclodextrin be explained by its hydration free energy alone?

The well-documented anomalous solubility of beta-cyclodextrin (beta-CD), relative to alpha- and gamma-CD, has been examined by Naidoo et al. (J. Phys. Chem. B, 2004, 108, 4236-4238.) from the perspective of water organization and internal motion of the macrocyclic rings. Whether modulation in the hydration patterns and in the rigidity of the molecular scaffold can be reconciled with the hydration free energy of beta-CD to rationalize its notorious low solubility remains open to further investigation. In this contribution, multi-nanosecond molecular dynamics (MD) simulations have been carried out to investigate the hydration process of alpha-, beta- and gamma-CD. The distribution of water molecules involved in this process and the linearity of intramolecular hydrogen bonds have been analyzed. The results reported here demonstrate that the anomalous solubility for beta-CD can be essentially rationalized by its greater rigidity conferred by the participating intramolecular hydrogen bonds and the higher density of water molecules of lesser mobility. The hydration free energy of alpha-, beta- and gamma-CD was computed using the free energy perturbation method. This quantity is shown to increase with the number of glucose units, thereby suggesting that the anomalous solubility of beta-CD cannot be explained by its free energy of hydration alone.     

Difference spatial distribution function analysis of aqueous solutions. III. Hydration structures of alcohol and ether solutions having straight chain and branched alkyl groups

Spatial distribution functions (SDFs), gOO(x,y,z) and gOH(x,y,z), obtained from Monte Carlo simulations at 298 K were applied to characterize the anisotropic structure of infinitely dilute aqueous solutions of alcohols and ethers having straight chain and branched alkyl groups. In spite of the different size and shape of the hydrophobic groups, the spatial orientation of the hydrogen-bonded water molecules was found to be of linear type with a triple layer structure in the hydrogen acceptor (HA) region and a double layer structure in the hydrogen donor (HD) region. The volumes and the coordination number (CN) in the HA region were essentially identical for all alcohol and ether solutions, but the volumes for the isopropyl alcohol (IPA) and isopropyl methyl ether (IPE) solutions were greater than those for the other solutions. In the hydrophobic hydration (HH) region, these values increased with increasing size and shape of hydrophobic groups, except in the case of IPA and IPE solutions. These results indicated that the hydration structures around the isopropyl group in alcohol and ether solutions differed from those in other solutions. From the results of the difference SDF (DSDF), AgOO(x,y,z), between SDFs gOO(x,y,z) for the two states, it was apparent that the distribution of hydration water molecules in the HA region for ether solution was characterized by the increase of the distribution in the direction of lone pair electrons on the oxygen atom of the solute molecule with increasing hydrophobicity.     

Difference spatial distribution function analysis of aqueous solutions. IV. Hydration structure changes of ethylene glycol solutions throughout conformational change process from gGg' to tGg' conformers

Monte Carlo (MC) simulations were carried out for an infinitely dilute aqueous solution of two stable conformers (gGg' and tGg') and of three conformations between gGg' and tGg' conformers of ethylene glycol (EG) at 298K. Based on the spatial distribution function (SDF) goo(x,y,z), obtained from the MC simulation in the above conformations in liquid water, the high distribution of hydration water molecules could be divided into hydrogen acceptor (HA), hydrogen donor (HD), MIX (overlapped distribution of HA and HD), and hydrophobic hydration (HH) regions. The spatial orientations of hydrogen-bonded water molecules were found to be of a linear type with a triple-layer structure in the HA region and HA part (in the MIX region), and double-layer structures in the HD region and HD part (in the MIX region). In addition, it was apparent that the spatial orientations of these water molecules were of the linear type throughout the conformational change process from gGg' to tGg' conformers in liquid water. From the difference SDF (DSDF), deltagoo(x,y, z), between the SDFs of two conformations, we concluded that the distribution of hydration water molecules in the HA and HD parts of the MIX region are governed by the competition of internal hydrogen bonds between the hydrogen atom and two lone-pair electrons on the oxygen atom of an EG molecule.     

Water-induced folding of 1,7-diammoniumheptane

Effects of hydration on the gaseous structures of diprotonated 1,7-diaminoheptane and protonated heptylamine are investigated by infrared photodissociation (IRPD) spectroscopy and computational chemistry. IRPD spectra in the hydrogen bond stretching region (2800-3900 cm(-1)) indicate that 1,7-diammoniumheptane is linear and that hydration occurs predominantly by alternate solvation of the two protonated amine groups for clusters with up to 10 water molecules. The relative intensities of bonded versus free hydroxyl (OH) stretches are greater in the spectra of 1,7-diammoniumheptane with more than 12 water molecules attached than the corresponding reference spectra of heptylammonium. This indicates that in the larger clusters, 1,7-diammoniumheptane adopts a more folded conformation in which the two protonated amine groups are solvated by a single water nanodrop. These results are supported by molecular dynamics simulations which show more hydrogen bonds in representative folded structures of hydrated 1,7-diammoniumheptane versus those with linear structures. These results indicate that the increase in Coulomb energy as a result of bringing the two positive charges closer together in the folded structures is compensated for by the additional hydrogen bonds that are possible when a single nanodrop solvates both protonated amine groups.     

Molecular dynamics study of the solvation of calcium carbonate in water

We performed molecular dynamics simulations of diluted solutions of calcium carbonate in water. To this end, we combined and tested previous polarizable models. The carbonate anion forms long-living hydrogen bonds with water and shows an amphiphilic character, in which the water molecules are expelled in a region close to its C(3) symmetry axis. The calcium cation forms a strongly bound ion pair with the carbonate. The first hydration shell around the CaCO(3) pair is found to be very similar to the location of the water molecules surrounding CaCO(3) in ikaite, the hydrated mineral.     

Hydrogen bond lifetime dynamics at the interface of a surfactant monolayer

The dynamics of water near the polar headgroups of surfactants in a monolayer adsorbed at the air/water interface is likely to play a decisive role in determining the physical behavior of such organized assemblies. We have carried out an atomistic molecular dynamics (MD) simulation of a monolayer of the anionic surfactant sodium bis(2-ethyl-1-hexyl) sulfosuccinate (aerosol-OT or AOT) adsorbed at the air/water interface. The simulation is performed at room temperature with a surface coverage of that at the critical micelle concentration (78 Angstrom(2)/molecule). Detailed analyses of the lifetime dynamics of surfactant-water (SW) and water-water (WW) hydrogen bonds at the interface have been carried out. The nonexponential hydrogen bond lifetime correlation functions have been analyzed by using the formalism of Luzar and Chandler, which allowed identification of the bound states at the interface and quantification of the dynamic equilibrium between bound and quasi-free water molecules, in terms of time-dependent relaxation rates. It is observed that the water molecules present in the first hydration layer form strong hydrogen bonds with the surfactant headgroups and hence have longer lifetimes. Importantly, it is found that the overall relaxation of the SW hydrogen bonds is faster for those water molecules which form two hydrogen bonds with the surfactant headgroups than those forming one such hydrogen bond. Equally interestingly, it is further noticed that water molecules beyond the first hydration layer form weaker hydrogen bonds than pure bulk water.     

Secondary structure sensitivity of hydrogen bond lifetime dynamics in the protein hydration layer

The heterogeneous nature of a protein surface plays an essential role in its biological activity and molecular recognition, and this role is mediated at least partly through the surrounding water molecules. We have performed atomistic molecular dynamics simulations of an aqueous solution of HP-36 to investigate the correlation between the dynamics of the hydration layer water molecules and the lifetimes of protein-water hydrogen bonds. The nonexponential hydrogen bond lifetime correlation functions have been analyzed by using the formalism of Luzar and Chandler, which allowed identification of the quasi-bound states in the surface and quantification of the dynamic equilibrium between quasi-bound and free water molecules in terms of time-dependent rate of interconversion. It is noticed that, irrespective of the structural heterogeneity of different segments of the protein, namely the three alpha-helices, the positively charged amino acid residues form longer-lived hydrogen bonds with water. The overall relaxation behavior of protein-water hydrogen bonds is found to differ significantly among the three helices of the protein. Study of water number density fluctuation reveals that the hydration layer of helix-3 is much less rigid, which can be correlated with faster structural relaxation of the hydrogen bonds between its residues and water. This also agrees excellently with faster translational and rotational motions of water near helix-3, and hence the lower rigidity of its hydration layer. The lower rigidity of the helix-3 hydration layer also correlates well with the biological activity of the protein, as several of the active-site residues of HP-36 are located in helix-3.     

Correlation between the dynamics of hydrogen bonds and the local density reorganization in the protein hydration layer

An atomistic molecular dynamics simulation of the protein villin headpiece subdomain or HP-36 has been carried out with explicit water to explore the microscopic inhomogeneity of local density reorganization of the hydration layers of the three alpha-helical segments of the protein. The density reorganization of the hydration layer of helix-3 is found to occur faster than that for the hydration layers of the other two helices. It is noticed that such inhomogeneous density reorganization at the surface of different secondary structures exhibits excellent correlation with the microscopic dynamics of hydrogen bonds between the protein residues and the hydration water. Further, it is observed that the reorientation of water molecules involved in the formation and breaking of protein-water or water-water hydrogen bonds plays an important role in determining the dynamics of local density of the hydration layer. The faster density reorganization of the hydration layer of helix-3 is also consistent with the functionality of HP-36, as helix-3 contains several active site residues.     

Molecular dynamics simulations of the hydration of poly(vinyl methyl ether):Hydrogen bonds and quasi-hydrogen bonds

Atomistic detailed hydration structures of poly(vinyl methyl ether)(PVME) have been investigated by molecular dynamics simulations under 300 K at various concentrations. Both radial distribution functions and the distance distributions between donors and acceptors in hydrogen bonds show that the hydrogen bonds between the polymer and water are shorter by 0.005 nm than those between water molecules. The Quasi-hydrogen bonds take only 7.2% of the van der Waals interaction pairs. It was found the hydrogen bonds are not evenly distributed along the polymer chain,and there still exists a significant amount(10%) of ether oxygen atoms that are not hydrogen bonded to water at a concentration as low as 3.3%. This shows that in polymer solutions close contacts occur not only between polymer chains but also between chain segments within the polymer,which leads to inefficient contacts between ether oxygen atoms and water molecules. Variation of the quasi-hydrogen bonds with the concentration is similar to that of hydrogen bonds,but the ratio of the repeat units forming quasi-hydrogen bonds to those forming hydrogen bonds approaches 0.2. A transition was found in the demixing enthalpy at around 30% measured by dynamic testing differential scanning calorimetry(DTDSC) for aqueous solutions of a mono-dispersed low molecular weight PVME,which can be related to the transition of the fractions of hydrogen bonds and quasi-hydrogen bonds at ～27%. The transition of the fractions of hydrogen bonds and quasi-hydrogen bonds at ～27% can be used to explain the demixing enthalpy transition at 30% at a molecular scale. In addition,at the concentration of 86%,each ether oxygen atom bonded with water is assigned 1.56 water molecules on average,and 'free' water molecules emerge at the concentration of around 54%.     

On the structure and dynamics of the hydrated sulfite ion in aqueous solution--an ab initio QMCF MD simulation and large angle X-ray scattering study

Theoretical ab initio quantum mechanical charge field molecular dynamics (QMCF MD) formalism has been applied in conjunction to experimental large angle X-ray scattering to study the structure and dynamics of the hydrated sulfite ion in aqueous solution. The results show that there is a considerable effect of the lone electron-pair on sulfur concerning structure and dynamics in comparison with the sulfate ion with higher oxidation number and symmetry of the hydration shell. The S-O bond distance in the hydrated sulfite ion has been determined to 1.53(1) ? by both methods. The hydrogen bonds between the three water molecules bound to each sulfite oxygen are only slightly stronger than those in bulk water. The sulfite ion can therefore be regarded as a weak structure maker. The water exchange rate is somewhat slower for the sulfite ion than for the sulfate ion, τ(0.5) = 3.2 and 2.6 ps, respectively. An even more striking observation in the angular radial distribution (ARD) functions is that the for sulfite ion the water exchange takes place in close vicinity of the lone electron-pair directed at its sides, while in principle no water exchange did take place of the water molecules hydrogen bound to sulfite oxygens during the simulation time. This is also confirmed when detailed pathway analysis is conducted. The simulation showed that the water molecules hydrogen bound to the sulfite oxygens can move inside the hydration shell to the area outside the lone electron-pair and there be exchanged. On the other hand, for the hydrated sulfate ion in aqueous solution one can clearly see from the ARD that the distribution of exchange events is symmetrical around the entire hydration sphere.     

Molecular simulation of the hydration Gibbs energy of barbiturates

In the present work, molecular dynamics calculations of the Gibbs energy of hydration of 10 different substituted barbiturates in SPC/E water were performed using thermodynamic integration. Given that experimental determination of the Gibbs hydration energy for this class of compounds is currently unfeasible, computer simulations appear as the only alternative for the estimation of this important quantity. Several simulation parameters are discussed and optimized based on calculations for barbituric acid. It is concluded that accounting for electrostatic interactions with the Reaction-Field method can be up to two times faster than with Particle-Mesh-Ewald method, without loss of accuracy. Different number of solvent molecules and simulation lengths were also tested. Lennard-Jones and electrostatic contributions were scaled down to zero in an independent way. It is shown that the electrostatic contribution is dominant (representing approximately 90% of the total Gibbs energy of hydration) and that barbiturate intra-molecular interactions cannot be neglected. The importance of the electrostatic contribution is attributed to the formation of hydrogen bonds between the barbiturates and water, which play an important role in the solvation process. The influence of the different substituents and their contribution to the Gibbs energy of hydration was assessed. Finally, the Lennard-Jones contributions and the total hydration Gibbs energy can both be correlated against molecular weight or partition coefficient data for mono- and di-substituted barbiturates.     

Ultrafast Vibrational Dynamics and Local Interactions of Hydrated DNA

Biochemical processes occur mainly in aqueous environments, where interactions with water molecules play a key role for both the structure and function of biomolecules. Deoxyribonucleic acid (DNA), the basic carrier of genetic information, is characterized by an equilibrium double helix structure which is held together by intermolecular hydrogen bonds between base pairs and hydrated by an environment of water molecules with fluctuating hydrogen bonds. Basic vibrational motions of hydrated DNA and the fastest changes in the DNA–water interactions and hydration geometries occur in less than 1 ps. These processes can be accessed by mapping the vibrational dynamics of DNA and water in a time‐resolved way by nonlinear ultrafast vibrational spectroscopy. Recent studies provide a detailed understanding of DNA vibrations and their dynamics, and give insight into nonequilibrium properties and structures of hydrated DNA.     

Hydration, swelling, interlayer structure, and hydrogen bonding in organolayered double hydroxides: insights from molecular dynamics simulation of citrate-intercalated hydrotalcite

Molecular dynamics (MD) simulation of the Mg/Al (3:1) layered double hydroxide (LDH), hydrotalcite (HT), containing citrate, C6H5O7(3-), as the charge balancing interlayer anion provides new molecular scale insight into the interlayer structure, hydrogen bonding, and energetics of the hydration and consequent swelling of LDH compounds containing organic and biomolecules. Citrate-HT exhibits affinity for water up to very high hydration levels, in contrast to the preferred low hydration states of most LDHs intercalated with small, inorganic anions. This result is consistent with the recent experimental observation of the delamination of lactate-HT. The high water affinity is rationalized in terms of the preference of citrate ion for hydrogen bonds (H-bonds) donated from water molecules rather than from the hydroxyl groups of the metal hydroxide layer and the need to develop an integrated interlayer H-bond network among the citrate ions, water, and -OH groups of the hydroxide layers. The changes in the orientation of citrate molecules with progressive hydration are also intimately related to its preference to accept hydrogen bonds from water.     

The hydration of glucose: the local configurations in sugar-water hydrogen bonds

The hydration of a simple sugar is an essential model for understanding interactions between hydrophilic groups and interfacial water molecules. Here I perform first-principles molecular dynamics simulations on a glucose-water system and investigate how individual hydroxyl groups are locally hydrated. I demonstrate that the hydroxyl groups are less hydrated and more incompatible with a locally tetrahedral network of hydrogen bonds than previously thought. The results suggest that the hydroxyl groups form roughly two hydrogen bonds. Further, I find that the local hydration of the hydroxyl groups is sensitively affected by seemingly small variations in the local electronic structure and bond polarity of the groups. My findings offer insight into an atomic-level understanding of sugar-water interactions.     

The effect of aqueous solutions of trimethylamine-N-oxide on pressure induced modifications of hydrophobic interactions

To understand the mechanism of protein protection by the osmolyte trimethylamine-N-oxide (TMAO) at high pressure, using molecular dynamics (MD) simulations, solvation of hydrophobic group is probed in aqueous solutions of TMAO over a wide range of pressures relevant to protein denaturation. The hydrophobic solute considered in this study is neopentane which is a considerably large molecule. The concentrations of TMAO range from 0 to 4 M and for each TMAO concentration, simulations are performed at five different pressures ranging from 1 atm to 8000 atm. Potentials of mean force are calculated and the relative stability of solvent-separated state over the associated state of hydrophobic solute are estimated. Results suggest that high pressure reduces association of hydrophobic solutes. From computations of site-site radial distribution function followed by analysis of coordination number, it is found that water molecules are tightly packed around the nonpolar particle at high pressure and the hydration number increases with increasing pressure. On the other hand, neopentane interacts preferentially with TMAO over water and although hydration of neopentane reduces in presence of this osmolyte, TMAO does not show any tendency to prevent the pressure-induced dispersion of neopentane moieties. It is also observed that TMAO molecules prefer a side-on orientation near the neopentane surface, allowing its oxygen atom to form favorable hydrogen bonds with water while maintaining some hydrophobic contacts with neopentane. Analysis of hydrogen-bond properties and solvation characteristics of TMAO reveals that TMAO can form hydrogen bonds with water and it reduces the identical nearest neighbor water molecules caused by high hydrostatic pressures. Moreover, TMAO enhances life-time of water-water hydrogen bonds and makes these hydrogen bonds more attractive. Implication of these results for counteracting effect of TMAO against protein denaturation at high pressures are discussed.     

Dynamics of halide ion-water hydrogen bonds in aqueous solutions: dependence on ion size and temperature

We have carried out a series of molecular dynamics simulations to investigate the dynamics of X(-)-water (X = F, Cl, Br, and I) and water-water hydrogen bonds in aqueous alkali halide solutions at room temperature and also of Cl(-)-water and water-water hydrogen bonds at seven different temperatures ranging from 238 to 318 K. The hydrogen bonds are defined by using a set of configurational criteria with respect to the anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)-oxygen-hydrogen angle for an anion(water)-water pair. The results of the hydrogen bond dynamics are obtained for two different cutoff values for the angular criterion. In both cases, similar dynamical behavior of the hydrogen bonds is found with respect to their dependence on ion size and temperature. The fluoride ion-water hydrogen bonds are found to break at a much slower rate than water-water hydrogen bonds, while the lifetimes of chloride and bromide ion-water hydrogen bonds are found to be shorter than those of fluoride ion-water ones but still longer than water-water hydrogen bonds. The short-time dynamics of iodide ion-water hydrogen bonds is found to be slightly faster, while its long-time dynamics is found to be slightly slower than the corresponding water-water hydrogen bond dynamics. Correlations of the observed dynamics of anion(water)-water hydrogen bonds with those of rotational and translational diffusion and residence times of water molecules in ion(water) hydration shells are also discussed. With variation of temperature, the lifetimes of both Cl(-)-water and water-water hydrogen bonds are found to show Arrhenius behavior with a slightly higher activation energy for the Cl(-)-water hydrogen bonds.     

High-density hydration layer of lysozymes: molecular dynamics decomposition of solution scattering data

A characterization of the physical properties of protein hydration water is critical for understanding protein structure and function. Recent small-angle X-ray and neutron scattering data indicate that the density of water on the surface of lysozyme is significantly higher than in bulk water. Here, we provide an interpretation of the scattering results using a molecular dynamics simulation, which allows us to make quantitative predictions about density variations in the first hydration shell. The perturbation relative to bulk water involves statistically significant changes in the average water structure in the first hydration layer. The water density in the first hydration shell is increased by 5% with respect to the bulk. In regions of higher water density, the water dipoles align more parallel to each other and the number of hydrogen bonds per water molecule is higher. Increased water density is found for water molecules interacting with hydrogen and carbon atoms in the backbone or with nonpolar or negatively charged side-chain groups.