All‐atom Molecular Dynamic Simulations Combined with the Chemical Shifts Study on the Weak Interactions of Ethanol‐water System

All‐atom molecular dynamics (MD) simulation combined with chemical shifts was performed to investigate the interactions over the entire concentration range of the ethanol (EtOH)‐water system. The results of the simulation were adopted to explain the NMR experiments by hydrogen bonding analysis. The strong hydrogen bonds and weak C–H···O contacts coexist in the mixtures through the analysis of the radial distribution functions. And the liquid structures in the whole concentration of EtOH‐water mixtures can be classified into three regions by the statistic analysis of the hydrogen‐bonding network in the MD simulations. Moreover, the chemical shifts of the hydrogen atom are in agreement with the statistical results of the average number hydrogen bonds in the MD simulations. Interestingly, the excess relative extent of η_rel^E calculated by the MD simulations and chemical shifts in the EtOH aqueous solutions shows the largest deviation at x_EtOH≈0.18. The excess properties present good agreement with the excess enthalpy in the concentration dependence.     

Solvation pressure in chloroform

Molecular dynamics (MD) simulations of chloroform vapor and liquid at normal temperature and pressure and liquid under hydrostatic pressure are presented, giving bond lengths and vibrational frequencies as functions of pressure. The change in bond lengths between vapor and liquid at normal temperature and pressure is consistent with a pressure equivalent to the cohesive energy density (CED) of the liquid, supporting the solvation pressure model which predicts that solvated molecules or nanoparticles experience a pressure equal to the CED of the liquid. Experimental data for certain Raman frequencies of chloroform in the vapor phase, in the liquid, and in the liquid under pressure are presented and compared to MD. Results for C-Cl vibrational modes are in general agreement with the solvation pressure model whereas frequencies associated with the C-H bond are not. The results demonstrate that masking interactions exist in the real liquid that can be reduced or eliminated in simplified simulations.     

Influence of bonded-phase coverage in reversed-phase liquid chromatography via molecular simulation I. Effects on chain conformation and interfacial properties

Particle-based Monte Carlo simulations were employed to examine the effects of bonding density on molecular structure in reversed-phase liquid chromatography. Octadecylsilane stationary phases with five different bonding densities (1.6, 2.3, 2.9, 3.5, and 4.2 mumol/m(2)) in contact with a water/methanol (50/50 mol%) mobile phase were simulated at a temperature of 323 K. The simulations indicate that the alkyl chains become more aligned and form a more uniform alkyl layer as coverage is increased. However, this does not imply that the chains are highly ordered (e.g., all-trans conformation or uniform tilt angle), but rather exhibit a broad distribution of conformations and tilt angles at all bonding densities. At lower densities, significant amounts of the silica surface are exposed leading to an enhanced wetting of the stationary phase. At high densities, the solvent is nearly excluded from the bonded phase and persists only near the residual silanols. An enrichment in the methanol concentration and a disruption in the mobile phase's hydrogen bond network are observed at the interface as bonding density is increased.     

Ultrafast 2D IR anisotropy of water reveals reorientation during hydrogen-bond switching

Rearrangements of the hydrogen bond network of liquid water are believed to involve rapid and concerted hydrogen bond switching events, during which a hydrogen bond donor molecule undergoes large angle molecular reorientation as it exchanges hydrogen bonding partners. To test this picture of hydrogen bond dynamics, we have performed ultrafast 2D IR spectral anisotropy measurements on the OH stretching vibration of HOD in D(2)O to directly track the reorientation of water molecules as they change hydrogen bonding environments. Interpretation of the experimental data is assisted by modeling drawn from molecular dynamics simulations, and we quantify the degree of molecular rotation on changing local hydrogen bonding environment using restricted rotation models. From the inertial 2D anisotropy decay, we find that water molecules initiating from a strained configuration and relaxing to a stable configuration are characterized by a distribution of angles, with an average reorientation half-angle of 10°, implying an average reorientation for a full switch of ≥20°. These results provide evidence that water hydrogen bond network connectivity switches through concerted motions involving large angle molecular reorientation.     

All-atom Molecular Dynamics Simulationsand NMR Spectroscopy Study on Interactions and Structures in N-Glycylglycine Aqueous Solution

All-atom molecular dynamics (MD) simulation and the NMR spectra are used to investi-gate the interactions in N-glycylglycine aqueous solution. Different types of atoms exhibit different capability in forming hydrogen bonds by the radial distribution function analysis. Some typical dominant aggregates are found in different types of hydrogen bonds by the statistical hydrogen-bonding network. Moreover, temperature-dependent NMR are used to compare with the results of the MD simulations. The chemical shifts of the three hydrogen atoms all decrease with the temperature increasing which reveals that the hydrogen bonds are dominant in the glycylglycine aqueous solution. And the NMR results show agreement with the MD simulations. All-atom MD simulations and NMR spectra are successful in revealing the structures and interactions in the N-glycylglycine-water mixtures.     

Molecular dynamics simulations of aqueous solutions of ethanolamines

We report on molecular dynamics simulations performed at constant temperature and pressure to study ethanolamines as pure components and in aqueous solutions. A new geometric integration algorithm that preserves the correct phase space volume is employed to study molecules having up to three ethanol chains. The most stable geometry, rotational barriers, and atomic charges were obtained by ab initio calculations in the gas phase. The calculated dipole moments agree well with available experimental data. The most stable conformation, due to intramolecular hydrogen bonding interactions, has a ringlike structure in one of the ethanol chains, leading to high molecular stability. All molecular dynamics simulations were performed in the liquid phase. The interaction parameters are the same for the atoms in the ethanol chains, reducing the number of variables in the potential model. Intermolecular hydrogen bonding is also analyzed, and it is shown that water associates at low water mole fractions. The force field reproduced (within 1%) the experimental liquid densities at different temperatures of pure components and aqueous solutions at 313 K. The excess and partial molar volumes are analyzed as a function of ethanolamine concentration.     

Stability of two-dimensional crystalline aggregates of a protein studied by molecular dynamics

Two-dimensional protein (ferritin) aggregates with a square lattice symmetry, which were formed within a thin liquid layer on a mercury surface, were studied by molecular dynamics (MD) simulation. For the simulation, the ferritin molecule was modeled by an assembly of 49 spheres, and the intermolecular interactions were given by simple formulae. During the simulation, molecules were confined within a layer, which corresponds to the thin liquid layer. An annealing MD simulation was done starting from a random molecular configuration within the layer, and aggregates with the square lattice symmetry were also obtained. To study the stability of aggregates, dissociation processes of the aggregates were analyzed using MD simulations at room temperature. Interactions between the nearest-neighbor molecules were regarded as bonds. Mean bond energies and correlation coefficients between the bond energies were calculated from the MD trajectories. A decay profile according to the dissociation was obtained, yielding a dissociation rate constant. Buried bonds were stronger than peripheral bonds. The larger the aggregate size, the stronger the bond for each of the buried and peripheral bonds. A simple theoretical account, which is applicable to a general bonded network, was introduced to analyze the dynamics of the aggregates. © 1994 by John Wiley & Sons, Inc.     

Influence of temperature on the structure of liquid water

Molecular dynamics simulations have been carried out for liquid water at 7 different temperatures to understand the nature of hydrogen bonding at molecular level through the investigation of the effects of temperature on the geometry of water molecules. The changes in bond length and bond angle of water molecules from gaseous state to liquid state have been observed, and the change in the bond angle of water molecules in liquid against temperature has been revealed, which has not been seen in literature so far. The analysis of the radial distribution functions and the coordinate numbers shows that, on an average, each water molecule in liquid acts as both receptor and donor, and forms at least two hydrogen bonds with its neigbors. The analysis of the results also indicates that the water molecules form clusters in liquid.     

Molecular dynamics simulations of heptyl phosphonic acid: a potential polymer component for fuel cell polymer membrane

Atomistic molecular dynamics simulations have been performed on heptyl phosphonic acid (HPA) to understand the dynamic hydrogen bonding network in the liquid phase. HPA is a phosphonic-acid functionalized alkane (heptane) and a model compound for one of the promising polymers for high temperature (>100 degrees C) fuel cell polymer electrolyte membranes. For the simulation, a force field for this molecule has been generated with the help of quantum chemical calculations and optimized by simplex algorithm. The force field has been validated against experimentally measured properties, for example, density and self-diffusion constant. From molecular dynamics simulations conducted at different temperatures, we have confirmed the hypothesis of dynamic hydrogen bond network formation in this material.     

Path Integral Molecular Dynamics of Liquid Water in a Mean-Field Particle Reservoir

We present a simulation scheme for path integral simulation of molecular liquids where a small open region is embedded in a large reservoir of non interacting point-particles. The scheme is based on the latest development of the adaptive resolution technique AdResS and allows for the space-dependent change of molecular resolution from a path integral representation with 120 degrees of freedom to a point particle that does not interact with other molecules and vice versa. The method is applied to liquid water and implies a sizable gain regarding the request of computational resources compared to full path integral simulations. Given the role of water as universal solvent with a specific hydrogen bonding network, the path integral treatment of water molecules is important to describe the quantum effects of hydrogen atoms’ delocalization in space on the hydrogen bonding network. The method presented here implies feasible computational efforts compared to full path integral simulations of liquid water which, on large scales, are often prohibitive.     

Terahertz time-domain spectra of aromatic carboxylic acids incorporated in nano-sized pores of mesoporous silicate.

Terahertz time-domain spectroscopy (THz-TDS) is used to study the intra- and intermolecular vibrational modes of aromatic carboxylic acids, for example, o-phthalic acid, benzoic acid, and salicylic acid, which form either intra- or intermolecular hydrogen bond(s) in different ways. Incorporating the target molecules in nano-sized spaces in mesoporous silicate (SBA-16) is found to be effective for the separate detection of intramolecular hydrogen bonding modes and intermolecular modes. The results are supported by an analysis of the differences in the peak shifts, which depend on temperature, caused by the different nature of the THz absorption. Raman spectra revealed that incorporating the molecules in the nano-sized pores of SBA-16 slightly changes the molecular structures. In the future, THz-TDS using nanoporous materials will be used to analyze the intra- and intermolecular vibrational modes of molecules with larger hydrogen bonding networks such as proteins or DNA.     

Liquid structures of water, methanol, and hydrogen fluoride at ambient conditions from first principles molecular dynamics simulations with a dispersion corrected density functional

Using first principles molecular dynamics simulations in the isobaric-isothermal ensemble (T = 300 K, p = 1 atm) with the Becke-Lee-Yang-Parr exchange/correlation functional and a dispersion correction due to Grimme, the hydrogen bonding networks of pure liquid water, methanol, and hydrogen fluoride are probed. Although an accurate density is found for water with this level of electronic structure theory, the average liquid densities for both hydrogen fluoride and methanol are overpredicted by 50 and 25%, respectively. The radial distribution functions indicate somewhat overstructured liquid phases for all three compounds. The number of hydrogen bonds per molecule in water is about twice as high as for methanol and hydrogen fluoride, though the ratio of cohesive energy over number of hydrogen bonds is lower for water. An analysis of the hydrogen-bonded aggregates revealed the presence of mostly linear chains in both hydrogen fluoride and methanol, with a few stable rings and chains spanning the simulation box in the case of hydrogen fluoride. Only an extremely small fraction of smaller clusters was found for water, indicating that its hydrogen bond network is significantly more extensive. A special form of water with on average about two hydrogen bonds per molecule yields a hydrogen-bonding environment significantly different from the other two compounds.     

Studies on the Structures and Hydrogen-bonding Interactions in Aqueous Glycine Solutions Using All-atom Molecular Dynamics Simulations and NMR Spectroscopy

All-atom molecular dynamics （MD） simulations and chemical shifts were used to study interactions and structures in the glycine-water system. Radial distribution functions and the hydrogen-bond network were applied in MD simulations. Aggregates in the aqueous glycine solution could be classified into different regions by analysis of the hydrogen-bonding network. Temperature-dependent NMR spectra and the viscosity of glycine in aqueous solutions were measured to compare with the results of MD simulations. The variation tendencies of the hydrogen atom chemical shifts and viscosity with concentration of glycine agree with the statistical results of hydrogen bonds in the MD simulations.     

Pressure and temperature dependence of the hydrogen bonding in supercritical ethanol: a computer simulation study

As a step toward deeper insight on the "hydrogen bonding" in supercritical ethanol (scEtOH), we carried out NVT molecular dynamics simulations of the fluid over a wide range of temperatures and pressures. The fluid was studied at SC conditions for which thermodynamic and spectroscopic (NMR, infrared, Raman, dielectric) data are available. The various site-site pair distribution functions (pdf's) were calculated, and their temperature and pressure dependence was obtained. It was found that over the thermodynamic conditions investigated here, scEtOH remains highly structured. Moreover, the characteristic behavior of the first peaks in H-H, O-O, and H-O pdf's reveals that hydrogen bonds still exist in scEtOH. The analysis focuses also on the reorientational dynamics of the bond unit vectors O-H, C-O, and of the permanent dipole moment of the molecules as well as the total dipole moment of the sample. The corresponding Legendre time correlation functions were discussed in connection to the "hydrogen bonding" in the fluid and in the context of experimental results. Specifically, the behavior of the O-H dynamics exhibits the well-known associative nature of the molecules in the system. A further analysis of the hydrogen bonds was carried out, and the degree of aggregation (average number of H-bonds per molecule) was obtained and compared with results from NMR chemical shift studies. Also the estimated monomer and free O-H groups in the fluid were compared with results from IR and Raman vibrational spectroscopy. The percentage analysis fi of the liquid and scEtOH molecules, with i = 0, 1, 2, 3, ... hydrogen bonds per molecule, has been obtained. The results show the existence of small, linear-chain oligomers formed mainly by two molecules, whereas the number of the three body oligomers, and specifically that of four body oligomers in the sample, is relatively small.     

特殊缔合体系TFE水溶液分子动力学模拟

三氟乙醇(TFE)水溶液是一类特殊的缔合体系. 采用分子动力学模拟方法结合核磁共振化学位移研究了TFE水溶液体系全浓度范围的氢键网络, 并对动力学模拟结果和核磁共振化学位移进行了比较. 从径向分布函数(RDF)发现, TFE水溶液中存在着强氢键, 而体系中的C—H…O弱相互作用较为明显, 也不能忽略. 氢键网络分析发现TFE 水溶液体系的氢键大致分为以下三个区域: 在水富集区域, 水分子倾向于自身缔合形成稳定的簇结构, 随着TFE 浓度的增加, 水的有序结构受到破坏, 水分子和TFE分子发生交叉缔合作用形成氢键; 在TFE富集区域, 水分子较少, TFE分子自身通过氢键形成多缔体结构. 此外, 分子动力学统计的平均氢键数的变化和文献报导的核磁共振化学位移变化趋势相同, 实验和理论的结果吻合较好.     

Nuclear quantum effects and hydrogen bonding in liquids

We have employed ab initio path integral molecular dynamics simulations to investigate the role of nuclear quantum effects on the strength of hydrogen bonds in liquid hydrogen fluoride. Nuclear quantum effects are shown to be responsible for a stronger hydrogen bond and an enhanced dipole-dipole interaction, which lead, in turn, to a shortening of the H...F intrachain distance. The simulation results are analyzed in terms of the electronic density shifts with respect to a purely classical treatment of the nuclei. The observed enhanced hydrogen-bond interaction, which arises from a coupling of intra- and intermolecular effects, should be a general phenomenon occurring in all hydrogen-bonded systems.     

Investigating pressure effects on structural and dynamical properties of liquid methanol with many-body interactions

Molecular-dynamics simulations utilizing a many-body potential was used to study the pressure dependence of structural and dynamical properties for liquid methanol. The liquid density as a function of pressure agreed well with experiment, and a combination of radial and angular distribution functions were used to analyze molecular structure. From these distribution functions, it was observed that hydrogen bond strength increased with increasing pressure. This observation coincided with an increase in the molecular dipole as a function of pressure, having a significant effect on the observed increased hydrogen bond strength. Also, methanols were found to more strongly favor exactly two hydrogen bonds, with fewer methanols of zero, one, or three hydrogen bonds present at higher pressures. Furthermore, a majority of the compression with increased pressure was found to occur in regions perpendicular to the methanol hydrogen-oxygen bond vector. This was the case despite hydrogen-oxygen nonbonded distances between hydrogen bonding species being shorter, but their stiffer oxygen-hydrogen-(nonbonded) oxygen angle offsets this, resulting in their oxygen-oxygen distances being relatively unaffected. The methanol translational diffusion decreased significantly with increased pressure, while the rotational diffusion decreased at a similar magnitude around the oxygen-hydrogen and oxygen-carbon bond vectors, despite having very different overall diffusion. Finally, the hydrogen bond lifetime increased significantly with pressure, owing to the increased hydrogen bond strength, and the slower translational and rotational dynamics.     

Structures and Hydrogen Bonding Interactions in Urea-water System Studied by All-atom MD Simulation and Chemical Shifts in NMR Spectrum

The interactions and structures of the urea-water system are studied by an all-atom molecular dynamics （MD） simulation. The hydrogen-bonding network and the radial distribution functions are adopted in MD simulations. The structures of urea-water mixtures can be classified into different regions from the analysis of the hydrogen-bonding network. The urea molecule shows the certain tendency to the self-aggregate with the mole fraction of urea increasing. Moreover, the results of the MD simulations are also compare with the chemical shifts and viscosities of the urea aqueous solutions, and the statistical results of the average number hydrogen bonds in the MD simulations are in agreement with the experiment data such as chemical shifts of the hydrogen atom and viscosity.     

Electronic structures and hydrogen bond network of high-density and very high-density amorphous ices

Electronic structures of hexagonal ice (ice Ih), high-density amorphous ice (HDA), and very high-density amorphous ice (VHDA) are investigated using ab initio density functional theory (DFT) at 77 K under a pressure of 0.1 MPa, focusing on band structure, density of states (DOS), partial density of states (PDOS), and electron density. It is found that the integration intensity of the O-2p bonding band in HDA is 1.53 eV wider than that in the VHDA. Because more 2p electrons in HDA participate the 2p-1s hybridization of O-H. The classical molecular dynamics (MD) method has further been carried out to analyze the hydrogen bond network of HDA and VHDA with larger numbers of water molecules under the same temperature, pressure, and boundary conditions used as those during the DFT calculation. MD results show that there exists some water molecules with five hydrogen bonds in both HDA (4.1 +/- 0.1%) and VHDA (2.8 +/- 0.1%), as compared with the LDA, being consistent with the integration intensity results of PDOS. This result can be used to interpret the physical nature of the similar transition temperature of HDA and VHDA to LDA with different heating rates.     

Molecular dynamics simulations of bovine cathepsin B and its complex with CA074

To promote our better understanding of the dynamic stability of the bovine cathepsin B structure, which is characterized by an extra disulfide bond at Cys148-Cys252 from the other species, and of the binding stability of CA074 (a cathepsin B-specific inhibitor), molecular dynamics (MD) simulations were performed for the enzyme and its CA074 complex, assuming a system in aqueous solution at 300 K. The MD simulation covering 400 ps indicated that the existence of a Cys148-Cys252 disulfide bond increases the conformational flexibility of the occluding loop, although the conformational stability of the overall structure is little affected. The structural characteristics of the complex elucidated by X-ray analysis were suggested to be also intrinsic and stable in the dynamic state; the hydrogen bonding/electrostatic interactions between the main and side chains of CA074 and the Sn and Sn' subsites of the enzyme were maintained throughout the MD simulation. Furthermore, the simulation made clear that the binding of CA074 significantly restricted the conformational flexibility of the substrate binding region, especially the occluding loop, of cathepsin B. Statistical analyses during the simulation suggest that the selectivity of CA074 for cathepsin B stems from the tight P1'-S1' and P2'-S2' interactions, assisted in particular by double hydrogen bonds between the carboxyl two oxygens of the CA074 C-terminus and the imidazole NH groups of His110 and His111 residues.