Investigations of peptide hydration using NMR and molecular dynamics simulations: A study of effects of water on the conformation and dynamics of antamanide

Summary The influence of water binding on the conformational dynamics of the cyclic decapeptide antamanide dissolved in the model lipophilic environment chloroform is investigated by NMR relaxation measurements. The water-peptide complex has a lifetime of 35 s at 250 K, which is longer than typical lifetimes of water-peptide complexes reported in aqueous solution. In addition, there is a rapid intracomplex mobility that probably involves librational motions of the bound water or water molecules hopping between different binding sites. Water binding restricts the flexibility of antamanide. The experimental findings are compared with GROMOS molecular dynamics simulations of antamanide with up to eight bound water molecules. Within the simulation time of 600 ps, no water molecule leaves the complex. Additionally, the simulations show a reduced flexibility for the complex in comparison with uncomplexed antamanide. Thus, there is a qualitative agreement between the experimental NMR results and the computer simulations.     

Understanding interaction and dynamics of water molecules in the epoxy via molecular dynamics simulation

The robust structural integrity of the epoxy plays an important role in ensuring the long-term service life of its applications, which is affected by the absorbed moisture. In order to understand the mechanism of the moisture effect, the knowledge of the interaction and dynamics of the water molecules inside the epoxy is of great interest. Molecular dynamics simulation is used in this work to investigate the structure and bonding behaviour of the water molecules in the highly cross-linked epoxy network. When the moisture concentration is low, the water molecules are well dispersed in the cross-linked structure and located in the vicinity of the epoxy functional groups, which predominantly form the hydrogen bond (H-bond) with the epoxy network, resulting in the low water mobility in the epoxy. At the high concentration, the water favourably forms the large cluster due to the predominant water–water H-bond interaction, and the water molecules diffuse primarily inside the cluster, which leads to the high water mobility and the accelerated H-bond dynamics. The variation of the bonding behaviour and dynamics of the water molecules reported here could be exploited to understand the material change and predict the long-term performance of the epoxy-based products during the intended service life.     

Structures and stability of salt-bridge in aqueous solution

Structures and stability of salt-bridges in aqueous solutions were investigated using a complex formed from the guanidinium (Gdm+) and formate (FmO-) ions as a model system. The Test-particle model (T-model) potentials to describe the interactions in the Gdm+-H2O, FmO(-)-H2O and Gdm+-FmO- complexes were constructed, tested and applied in molecular dynamics (MD) simulations of the aqueous solutions at 298 K. The three-dimensional structures and energetic of the hydrogen bond (H-bond) networks of water in the first hydration shells of the Gdm+ and FmO- ions, as well as the Gdm+-FmO- complex, were visualized and analyzed using various probability distribution (PD) maps. The structures of the average potential energy landscapes at the H-bond networks were employed to characterize the stability and dynamic behavior of water molecules in the first hydration shells of the solutes. It was observed that water molecules in the first hydration shell of the close-contact Gdm+-FmO- complex form associated H-bond networks, which introduce a net stabilization effect to the ion-pair, whereas those in the interstitial H-bond network destabilize and break the solvent-separated Gdm+-FmO- complex. The present results showed that, in order to provide complete insights into the structures and stability of ion-pairs in aqueous solutions, explicit water molecules have to be included in the model calculations.     

Microstructures,interactions and dynamics properties studies of N-methyldiethanolamine + guanidinium triflate ionic liquid + water tertiary system at the standard temperature

Molecular dynamics simulations with an all-atom force field have been carried out in order to understand the phase equilibrium behaviour of ternary aqueous mixtures containing guanidinium triflate ionic liquid [gua][OTf] and water mixed with N-methyldiethanolamine (MDEA) in different function composition at the standard temperature of 298.15 K. A very good numerical agreement has been obtained for the prediction of the mixture densities. The analysis of structural and dynamic properties showed that the molecular level of ternary mixtures is slightly affected by the presence of MDEA and [gua][OTf] molar fractions. For MDEA–water interactions in [gua][OTf] media, we found that MDEA prefers to be surrounded by water molecules rather than by MDEA molecules even at a high MDEA molar fraction. While for [gua][OTf]–water interaction in MDEA media, as [gua][OTf] molar fraction increases, water molecules replace counterions in the coordination shell of both ions, thus weakening their interaction. On the other hand, for MDEA–[gua][OTf] interactions in water media, we have found that as the molar fraction of [gua][OTf] increases, a sulfonate group from anion appears to have a stronger association by making hydrogen bonding with MDEA molecules. The chemical process using ionic liquids (ILs) as solvents is commonly limited by their high viscosity. Based on their physical properties such as viscosities, these ternary solvents can be applied in natural gas industry, such as removing carbon dioxide using aqueous MDEA and IL at high pressure.     

Hydrogen bond analysis of confined water in mesoporous silica using the reactive force field

ABSTRACT

The structural and dynamical properties of water confined in nanoporous silica with a pore diameter of 2.7?nm were investigated by performing large-scale molecular dynamics simulations using the reactive force field. The radial distribution function and diffusion coefficient of water were calculated, and the values at the centre of the pore agreed well with experimental values for real water. In addition, the pore was divided into thin coaxial layers, and the average number of hydrogen bonds, hydrogen bond lifetime and hydrogen bond strength were calculated as a function of the radial distance from the pore central axis. The analysis showed that hydrogen bonds involving silanol (Si–OH) have a longer lifetime, although the average number of hydrogen bonds per atom does not change from that at the pore centre. The longer lifetime, as well as smaller diffusion coefficient, of these hydrogen bonds is attributed to their greater strength.     

Computer Simulation of Liquid Methanol II. System Size Effects

Abstract

A series of molecular dynamics simulations of liquid methanol has been carried out on a supernode transputer array. Four system sizes from 125 to 512 molecules have been considered, in order to study the effect of system size on the calculated structural, orientational and dynamic properties. The dielectric constant and the dielectric relaxation time are compared with experimental data.     

On singularities of molecular relaxation in water solutions

In this paper, we analyzed spectra of liquid water and water solutions in a frequency domain, characteristic of the collective dynamics of water molecules (from 0 to 200 cm^?1). Particular attention is paid to the relaxation processes, one of which is observed in the terahertz region of the spectrum (～5–50 cm^?1). The physical essence of this process at the molecular level is still unclear. Based on data obtained this process is strongly suggested to interpret as a monomolecular relaxation of unbound water molecules.     

Molecular Dynamics Study of Water in Hydrogels

Abstract

Molecular dynamics simulations are performed for aqueous solutions of polymers: Poly (vinyl alcohol) (PVA), Poly (vinyl methylether) (PVME), and Poly (N-isopropyl acrylamide) (PNiPAM). The distributions and dynamics of hydrogen-bonds, the translational diffusion of water, and the orientational relaxation of water are analyzed to investigate the properties of water which is highly influenced by the surrounding polymer chains. The water molecules around the polymer chains are highly hindered by the chains.     

Leucine 41 is a gate for water entry in the reduction of Clostridium pasteurianum rubredoxin

Biological electron transfer is an efficient process even though the distances between the redox moieties are often quite large. It is therefore of great interest to gain an understanding of the physical basis of the rates and driving forces of these reactions. The structural relaxation of the protein that occurs upon change in redox state gives rise to the reorganizational energy, which is important in the rates and the driving forces of the proteins involved. To determine the structural relaxation in a redox protein, we have developed methods to hold a redox protein in its final oxidation state during crystallization while maintaining the same pH and salt conditions of the crystallization of the protein in its initial oxidation state. Based on 1.5 A resolution crystal structures and molecular dynamics simulations of oxidized and reduced rubredoxins (Rd) from Clostridium pasteurianum (Cp), the structural rearrangements upon reduction suggest specific mechanisms by which electron transfer reactions of rubredoxin should be facilitated. First, expansion of the [Fe-S] cluster and concomitant contraction of the NH...S hydrogen bonds lead to greater electrostatic stabilization of the extra negative charge. Second, a gating mechanism caused by the conformational change of Leucine 41, a nonpolar side chain, allows transient penetration of water molecules, which greatly increases the polarity of the redox site environment and also provides a source of protons. Our method of producing crystals of Cp Rd from a reducing solution leads to a distribution of water molecules not observed in the crystal structure of the reduced Rd from Pyrococcus furiosus. How general this correlation is among redox proteins must be determined in future work. The combination of our high-resolution crystal structures and molecular dynamics simulations provides a molecular picture of the structural rearrangement that occurs upon reduction in Cp rubredoxin.     

Molecular dynamics simulation of liquid water under the influence of an external electric field

Molecular dynamics simulations of liquid water were performed at 258K and a density of 1.0?g/cm³ under various applied external electric field, ranging 0～10¹⁰?V/m. The influence of external field on structural and dynamical properties of water was investigated. The simple point charge (SPC) model is used for water molecules. An enhancement of the water hydrogen bond structure with increasing strength of the electric field has been deduced from the radial distribution functions and the analysis of hydrogen bonds structure. With increasing field strength, water system has a more perfect structure, which is similar to ice structure. However, the electrofreezing phenomenon of liquid water has not been detected since the self-diffusion coefficient was very large. The self-diffusion coefficient decreases remarkably with increasing strength of electric field and the self-diffusion coefficient is anisotropic.     

Molecular dynamics simulations of microstructure and mixing dynamics of cryoprotective solvents in water and in the presence of a lipid membrane

Molecular dynamics (MD) simulation is used to investigate the solubility behavior of cryoprotective (CP) solvents, such as DMSO, ethylene glycol (EG) and glycerol (GL), in pure water and in the presence of a lipid membrane. The MD study is focused on an equilibration timescale required for mixing large CP aggregates with aqueous and aqueous/lipid environments. The MD analysis demonstrates that DMSO mixes rapidly with water, so that all solute molecules are uniformly distributed in the equilibrium aqueous solution. Our investigation of the microstructure of binary EG/water and GL/water systems reveals that, despite the miscibility of both CP solvents with water, they are not ideally mixed in aqueous solutions at the molecular level. The MD simulations show that the mixing dynamics of the large CP cluster and surrounding water is found to be strongly dependent on nature of hydrophilic and hydrophobic interactions acting between cryoprotectant molecules. In particular, a spatial hydrogen-bond network formed between CP molecules plays an important role in the mixing dynamics between CP agents and water. A further analysis on the mixing behavior of the CP solvents with pure water and with aqueous solutions at a lipid membrane interface shows that, due to strong binding of the CP molecules to membrane surface, the equilibration process in the lipid environment becomes very slow, at least of the order of microseconds. The MD results are discussed in the context of the better understanding on the composition of the aqueous mixtures of the EG and GL solvents. Knowledge of the microstructure and the dynamics of these systems helps to develop better cryopreservation protocols and to propose more optimal cooling/warming regimes for cellular cryosolutions.     

Dielectric spectroscopy study of myoglobin in glycerol-water mixtures

Due to the interest in protein dynamics, there are numerous dielectric relaxation studies of proteins in water and in glass-forming aqueous solvents such as glycerol-water mixtures. In the regime of low frequencies, the inevitable dc-conductivity of such systems limits the resolution of dynamics that are slow compared with the solvent relaxation. Solutions of myoglobin in glycerol/water mixtures of various compositions are measured by dielectric spectroscopy in the frequency range from 10 mHz to 10 MHz. The resolution of low frequency modes is improved by two approaches: electrical ‘cleaning’ and the analysis of the derivative of the real component of permittivity, which shows no direct signature of dc-conductivity. Effects of internal interfacial polarization are also addressed by measuring the same solvents in confinement as well as mixed with glass beads. We find two processes, the structural relaxation of the solvent and the slower rotational mode of the protein, with no indication at even lower frequencies of a dielectric signature of fluctuations associated with protein dynamics.     

The role of protein–solvent hydrogen bond dynamics in the structural relaxation of a protein in glycerol versus water

We used MD simulations to investigate the dependence of the dynamics of a soluble protein, RNase A, on temperature and solvent environment. Consistent with neutron scattering data, the simulations predict that the protein undergoes a dynamical transition in both glycerol and aqueous solutions that is absent in the dry protein. The temperature of the transition is higher, while the rate of increase with temperature of the amplitudes of motion on the 100 ps timescale is lower, in glycerol versus water. Analysis of the dynamics of hydrogen bonds revealed that the protein dynamical transition is connected to the relaxation of the protein-solvent hydrogen bond network, which, in turn, is associated with solvent translational diffusion. Thus, it appears that the role of solvent dynamics in affecting the protein dynamical transition is qualitatively similar in water and glycerol.     

Hydration structure and dynamics of B- and Z-DNA in the presence of counterions via molecular dynamics simulations

Following our previous attempts at understanding the structural and dynamical properties of water and counterions hydrating nucleic acids, we have performed molecular dynamics simulations for B- and Z-DNA. In these simulations, the nucleic acids were held rigid. In the case of B-DNA, one turn of B-DNA double helix was considered in the presence of 1500 water molecules and 20 counterions (K⁺). The simulations were performed for 4.0 ps after equilibrating the system. For Z-DNA, we considered one turn of the double helix in the presence of 1851 water molecules and 24 counterions (K⁺). The simulations were carried out for 3.5 ps after equilibration. The average temperature of these simulations was ～ 360 K for Z-DNA and ～ 345 K for B-DNA. In these simulations the hydrogen atoms were explicitly taken into account. For both simulations, a fifth-order predictor-corrector was used for solving the translational equations of motion. The rotational motion of the water molecules was represented in terms of quaternion algebra and the rotational equations of motion were solved with a second-order quaternion method using a sixth-order predictor-corrector method. A time step of 0.5 · 10^?15 s was used in these simulations. The structural and the dynamical properties of water solvating the counterions, and the phosphate groups of the DNA, were computed to understand the hydration structure. Diffusion coefficients and velocity correlation functions were calculated for both ions and the water molecules. The velocity correlation functions for the ions exhibit a caged behavior. The dipole correlation functions for the water molecules indicate that the water molecules close to the helix retain the memory of their initial orientations for longer periods of time than those away from the helix. During the time period of our simulation (3–4 ps) the ion probability distributions show a well-defined pattern and suggest limited mobility for the ions, being close to the helix.     

THz frequency spectrum of protein–solvent interaction energy using a recurrence plot‐based Wiener–Khinchin method

The dynamics of a protein and the water surrounding it are coupled via nonbonded energy interactions. This coupling can exhibit a complex, nonlinear, and nonstationary nature. The THz frequency spectrum for this interaction energy characterizes both the vibration spectrum of the water hydrogen bond network, and the frequency range of large amplitude modes of proteins. We use a Recurrence Plot based Wiener–Khinchin method RPWK to calculate this spectrum, and the results are compared to those determined using the classical auto‐covariance‐based Wiener–Khinchin method WK. The frequency spectra for the total nonbonded interaction energy extracted from molecular dynamics simulations between the β‐Lactamase Inhibitory Protein BLIP, and water molecules within a 10 Å distance from the protein surface, are calculated at 150, 200, 250, and 310 K, respectively. Similar calculations are also performed for the nonbonded interaction energy between the residues 49ASP, 53TYR, and 142PHE in BLIP, with water molecules within 10 Å from each residue respectively at 150, 200, 250, and 310 K. A comparison of the results shows that RPWK performs better than WK, and is able to detect some frequency data points that WK fails to detect. This points to the importance of using methods capable of taking the complex nature of the protein–solvent energy landscape into consideration, and not to rely on standard linear methods. In general, RPWK can be a valuable addition to the analysis tools for protein molecular dynamics simulations. Proteins 2016; 84:1549–1557. © 2016 Wiley Periodicals, Inc.     

On the properties of aqueous amide solutions through classical molecular dynamics simulations

The structure and dynamics of infinitely diluted aqueous amide solutions is studied for 13 compounds in the NVT ensemble using classical molecular dynamics simulations. The aim of this work is to provide valuable insights into the effect of amides on liquid water properties in order to understand the amides role in the kinetic inhibition of clathrate hydrate formation in natural gas mixtures. The OPLS-AA forcefield is used to describe the amides, with parameters obtained through fitting of computed B3LYP/6-311++g^{* *} data when not available in the literature, and the SPC-E model is applied for water molecules. Structural properties of the solutions are analyzed via calculated radial distribution functions and dynamic properties are studied with the computed mean square displacements and velocity autocorrelation functions. Most of the studied compounds show a remarkable structuring effect on the surrounding water with strong interactions resulting from hydrogen bonding between solute and solvent molecules. Hydrophobic and hydrophilic synergistic effects influence the amide–water interaction and the properties of the water solvation shells around amides.     

Protective mechanisms of α,α-trehalose revealed by molecular dynamics simulations

Molecular dynamics simulations were carried out to model aqueous solution with different concentration of α,α-trehalose, one kind of non-reducing sugars possessing outstanding freeze-drying protective effect on biological system. The dihedral angles of the intraglycosidic linkage in trehalose were measured to estimate its structure rigidity. The dynamics and hydrogen bonding properties were studied by calculating the self-diffusion coefficient of trehalose and the distributions and lifetimes of various types of H-bonds in the solution. Through analysing the results as well as comparison with another common sugar sucrose, the freeze-drying protective mechanism of trehalose was explained at molecule level. First, trehalose is able to maintain the local structure around it as a frame due to its relatively rigid conformation. Second, the addition of trehalose restrains the water molecules from rearrangement as a result of low mobility, thus reduces the probability of freezing; trehalose has lower diffusion coefficient than water and bigger thermal diffusivity, which are favourable for vitrification. Third, the formation of H-bonds between trehalose and water and between trehalose molecules is the essence of the protective effect. Trehalose does not work via strengthening the H-bonds formed between water molecules (W–W H-bonds), instead of which it breaks the potential tetrahedral pattern of W–W H-bonds, thus suppresses the tendency of ice formation. It was also found that trehalose realises protective action better at higher concentration as far as this study is concerned.     

Effects of metal ion and solute conformation change on hydration of small amino acid

The effects of metal ion and solute conformation change on the structures, energetic and dynamics of water molecules in the first hydration shell of amino acid were studied, using three forms of alanine (Ala) and Li(+)/Ala as model molecules. The theoretical investigations were started with construction of the test-particle model (T-model) potentials for all molecules involved and followed by molecular dynamics (MD) simulations of [Ala](aq) and [Li(+)/Ala](aq) at 298 K. The MD results showed that the hydrogen bond (H-bond) networks of water at the functional groups of Ala are strengthened by the metal ion binding, whereas the rotation of the N-C(alpha) bond from the angle phi=0 degrees to 180 degrees brings about smaller effects which cannot be generalized. It was also shown that the dynamics of water molecule in the first hydration shell of amino acid could be estimated from the total-average potential energy landscapes and the water exchange diagrams. The MD results suggested inclusion of an additional dynamic step in the water exchange process, in which water molecule moves inside a channel within the first hydration shell of solute, before leaving the channel at some point. The theoretical results reported in the present work iterated the necessity to include explicit water molecules in the model calculations.     

Dynamics of vibrational frequency fluctuations in deuterated liquid ammonia: roles of fluctuating hydrogen bonds and free ND modes

We present an ab initio molecular dynamics study of the roles of fluctuating hydrogen bonds and free ND modes in the dynamics of ND stretch frequency fluctuations in deuterated liquid ammonia. We have also looked at some of the other dynamical quantities such as diffusion and orientational relaxation and also structural quantities such as pair correlations and hydrogen bonding properties which are relevant in the current context. The time correlation function of ND stretch frequencies is found to decay with primarily two time scales: A short-time decay with a time scale of less than 100 fs arising from intermolecular motion of intact hydrogen bonds and also from fast hydrogen bond breaking and a longer time scale of about 500 fs which can be assigned to the lifetime of free ND modes. Unlike water, in liquid ammonia an ND mode is found to remain free for a longer period than it stays hydrogen bonded and this longer lifetime of free ND modes determines the long-time behaviour of frequency fluctuations. Our hole dynamics calculations produced results of vibrational spectral diffusion that are similar to the decay of frequency time correlation. Inclusion of dispersion corrections is found to make the dynamics slightly faster.