Dynamics Of Aqueous Solutions Research Articles

MC-PHS: A Monte Carlo Implementation of the Primary Hydration Shell for Protein Folding and Design

A primary hydration shell (PHS) approach is developed for Monte Carlo simulations of conformationally rich macromolecular systems in an environment that efficiently captures principal solvation effects. It has been previously demonstrated that molecular dynamics using PHS is an efficient method to study peptide structure and dynamics in aqueous solution. Here, we extend the PHS approach to Monte Carlo simulations, whereby a stable shell of water molecules is maintained with a flexible, nonspherical, half-harmonic potential, tuned to maintain a constant restraining energy, with the difference between the restraint and shell energies used to dynamically adjust the shell radius. Examination of the shell and system size dependence of the restraining potential reveals its robustness. Moreover, its suitability for biomolecular simulations is evaluated using small spheres of water, hydration properties of small biological molecules, and configurational sampling of β-hairpin pentapeptide YPGDV. This method, termed MC-PHS, appears to provide efficient representation of dominant solvation effects and should prove useful in the study of protein folding and design.

Dynamics in aqueous solutions of poly(vinyl alcohol) and its hydrophobically modified anionic analogues

The dynamics of aqueous solutions of unmodified poly(vinyl alcohol) (PVA) and of hydrophobically modified anionic analogues with two different degrees of hydrophobic substitution (HMPVA1 and HMPVA2) is studied with the aid of viscometry and dynamic light scattering (DLS). The viscosity results reveal a pronounced polyelectrolyte effect in dilute solutions of HMPVA1, while strong association effects, even at very low concentrations, are observed in solutions of the analogue with the highest hydrophobicity. The relaxation times for solutions of PVA are practically independent of concentration over the considered range. For the hydrophobically modified analogues, both the fast and the slow relaxation times increase with increasing concentration for both systems, but the concentration dependencies of the relaxation times are much stronger for HMPVA2 due to enhanced hydrophobic associations.

Computer simulation studies of the structure and dynamics of ions and non–polar solutes in water

The mobility of simple ions such as alkali–metal and halide ions at room temperature shows two anomalies. Firstly, there are maxima in mobilities as a function of ion size for both positive and negative ions and, secondly, the maximum for negative ions occurs at a larger ionic radius than the maximum for positive ions. Theoretical treatments of this problem are reviewed and it is concluded that a molecular treatment of the system is needed to understand the results. Computer simulation using the simple point charge model (SPC/E) for water reproduced the observations and is used to discuss the application of theories. In particular, the nature of the first solvation shell is correlated with ion mobility. Simulation reveals a further anomaly, namely that if the charge is removed from a large ion, then it moves more slowly. This is interpreted as the result of formation of a solvent cage around the hydrophobic solute. The changes in local structure resulting from changes in charge and size also affect the solvation thermodynamics. Simulations show that the solvation entropy has a double maximum when viewed as a function of charge. The local minimum near zero charge is interpreted as being due to hydrophobic order, and the maxima as the result of structure breaking. This double maximum in the entropy of solvation is a signature of the hydrophobic cage effect. Comparisons are made between ion mobilities in liquid water at ambient and supercritical conditions.

Cu(II) solvate complex dynamics in aqueous solutions of LiCl at low temperature.

Cu(II) solvate complex dynamics in aqueous solutions of LiCl at low temperature.

Structure and dynamics of a DNA duplex containing single alpha-anomeric deoxyadenosine residue.

Structure and dynamics of an undecamer DNA duplex containing a single alpha-anomeric deoxyadenosine residue placed in opposition to a thymidine unit have been studied using simulation of molecular dynamics in aqueous solution. Despite several noticeable deviations from the B-DNA duplex structure caused by the anomerisation, such as: West type puckering of the alpha-anomeric sugar, disrupted base stacking pattern and unstable duplex bending, the formation of a non-classical alpha-dA-T pair was observed. A novel way of visual presentation of trajectory data allowing high throughput screening of the conformational parameters is presented.

Diffusive Dynamics of Water in the Presence of Homologous Disaccharides: A Comparative Study by Quasi Elastic Neutron Scattering. IV.

The present paper reports on the study of the disaccharides' dynamics in aqueous solutions and discusses the role of their interaction with water, which seems to be responsible for the protective action on biological membranes and tissues. In particular, using QENS (IRIS at ISIS, RAL, U.K.) we compared the quasielastic spectra from three homologous disaccharides (trehalose, maltose, and sucrose) with a hydration of 20 water molecules per each disaccharide molecule. The isotopic substitution method allowed us to study also the dynamics of water in the presence of the disaccharides. Our results show that trehalose is the most effective in slowing down the water dynamics, inducing a more extensive hydration layer.

Modeling the Cementation Dynamics in Aqueous Solutions in the Absence of Hydrogen Evolution

A modeling description of the process of deposition of a nobler metal from an aqueous solution, which involves no hydrogen evolution, is considered. On the basis of the balance between anodic and cathodic currents and with use made of the idea about a mixed control of the metal reduction on the growing-nuclei tips, a set of differential equations is constructed, which is solved by the Runge–Kutta method in the Mathcad Plus 6 format. Examples of the cementation dynamics at different balance between exchange currents of components and different solution depletion rates by ions of the deposited metal are considered.

Influence of substituents on the solution conformation of the exopolysaccharide produced by Pseudomonas ‘gingeri’ strain Pf9

The influence of pyruvate ketals and acetyl groups on the conformational behaviour of the exopolysaccharide produced by Pseudomonas ‘gingeri’ strain Pf9 has been investigated experimentally through studies of intrinsic viscosity and circular dichroism experiments. A conformational variation was detected as a function of the ionic strength. Measurements carried out on the native polymer, as well as on both de-pyruvated and de-acetylated samples, suggested a critical role for the acetyl group on the solution conformation of the polysaccharide. Molecular mechanics calculations indicated the possibility of intramolecular hydrogen bonding between acetyl substituents on the mannose and the C(2)OH group of the preceding saccharidic unit. NMR linewidth measurements, carried out as a function of temperature, on the low molecular weight de-pyruvated sample indicated different polymeric backbone dynamics in aqueous solutions with respect to that observed in 0.3 M NaCl solutions.

Effect of solvent fluctuations on proton transfer dynamics: a hybrid AM1/MM molecular dynamics simulation on the [H3N–H–NH3]+ system

Abstract Combined AM1/TIP3P Molecular Dynamics simulations have been carried out to investigate proton transfer dynamics in aqueous solution for the proton-bound ammonia dimer model system. The distance between nitrogen atoms has been fixed to 2.62 A so that proton transfer events occur every 10–20 ps in average. The chemical reaction is clearly shown to be preceded by a solvent fluctuation which starts about 700 fs before reaching the transition structure.

Micellar Dynamics in Aqueous Solutions of PEO−PPO−PEO Block Copolymers

The dynamics of poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) micelle rearrangements were studied using iodine laser temperature jump experiments with light-scattering detection. Two relaxation processes were detected: the first, fast one was accompanied by an increase in scattered light intensity, while the second, slow process was accompanied by a reduction in light intensity. The Aniansson−Wall theory was used to interpret the experimental results. The equilibrium micelle structures at the start and end points of the temperature jump experiment were used as input for the Aniansson−Wall equations. The solution of these equations agrees qualitatively with experimental data and suggests the mechanisms associated with the two time constants. The first time scale, in the tens of microseconds to about 10 ms range, is attributed to unimer insertion into micelles. The other time scale, in the 1−100 ms range, is associated with the rearrangement of the micelle size distribution. It is shown that the second process is often not observed either because the unimer supply is insufficient or because the micelle number density is not temperature dependent.

Observation of the A-DNA to B-DNA Transition During Unrestrained Molecular Dynamics in Aqueous Solution

A large challenge in molecular dynamics (MD) simulations of proteins and nucleic acids is to find the correct “experimental” geometry when a simulation is started a significant distance away from it. In this study, we have carried out four unrestrained ≈1 ns length MD trajectories in aqueous solution on the DNA duplex d(CCAACGTTGG) 2, two beginning in a canonical A-DNA structure and two beginning in a canonical B-DNA structure. As judged by root-mean-squared coordinate deviations, average structures computed from all four of the trajectories converge to within ≈0.8 to 1.6 Å (all atoms) of each other, which is 1.3 to 1.7 Å (all atoms of the central six residues from each strand) and 3.1 to 3.6 Å (all atoms) away from the B-DNA-like X-ray structure reported for this sequence. To our knowledge, this is the first example of multiple nanosecond molecular dynamics trajectories with full representation of DNA charges, solvent and long range electrostatics that demonstrate both internal consistency (two different starting structures and four different trajectories lead to a consistent average structure) and considerable agreement with the X-ray crystal structure of this sequence and NMR data on duplex DNA in aqueous solution. This internal consistency of structure for a given sequence suggests that one can now begin to realistically examine sequence-dependent structural effects in DNA duplexes using molecular dynamics.

Protein hydration dynamics in aqueous solution.

Water oxygen-17 and deuteron spin relaxation rates, measured as a function of resonance frequency, have been used to study the dynamics of protein hydration in aqueous solutions of ribonuclease A, lysozyme, myoglobin, trypsin and serum albumin. The relaxation data conform to the picture of protein hydration dynamics, proposed on the basis of previous studies of smaller proteins, where the long-lived water molecules responsible for the relaxation dispersion are identified with a small number of integrat water molecules seen in the crystal structures. These integral water molecules, with residence times in the range 10(-9)-10(-3) s, are either buried in internal cavities, trapped in narrow clefts or coordinated to metal ions. For the water molecules in the traditional hydration layer at the protein surface, the relaxation data suggest an average residence time in the range 10-50 ps, consistent with high-resolution 1H spectroscopy and computer simulations. The relaxation data also reveal some more specific features of protein hydration, relating to hydration of cavities that appear empty by crystallography, entrapment of water between structural domains of large proteins and subnanosecond 180 degrees flips in buried water clusters.

A Nuclear Magnetic Relaxation Study of the Dynamics of NO3− and SCN− Ions in Liquid Ammonia

Abstract A nuclear magnetic relaxation study of the rotational dynamics of nitrate and thiocyanate anions in 1 M solutions of liquid ammonia is presented. For both anions D⊥ was determined and shown to be larger than observed in aqueous solution. The rotational anisotropy of the nitrate ion was found to be temperature dependent (233—303 K). Thiocyanate ion 13C relaxation was found to be dominated by the spin rotation mechanism. The overall dynamics of both ions is shown to be less restricted in liquid ammonia compared to their dynamics in aqueous solutions.

The structure and dynamics of aqueous solutions containing complex molecules

Neutron scattering techniques and isotopic substitution have been used successfully to study the nature of hydration in simple aqueous solutions. In this paper we discuss how these techniques have been extended to studies of hydration phenomena in systems containing large polymeric molecules.

Dynamics in aqueous solutions of the pentasaccharide corresponding to the binding site of heparin for antithrombin III studied by NMR relaxation measurements

1H NMR and 13C NMR relaxation measurements at different magnetic field strengths were used to study the nature of overall and internal motions, in aqueous solution, of the synthetic pentasaccharide (A-G-A ∗-I-A M) corresponding to the binding site of heparin for antithrombin III. Two-dimensional double INEPT spectra were recorded at 11.7 T with and without suppression of cross-correlation effects between dipolar and chemical shift anisotropy relaxation mechanisms in measurements of spin-lattice and spin-spin relaxation times. Moreover, longitudinal relaxation times were collected at 7 T with the inversion recovery method. One dimensional NOESY spectra were recorded at 11.7 T and 9.4 T with various mixing times when spins of the A1 ∗ and A4 ∗ protons were inverted in the central residue of the pentasaccharide. Differences in the T 1 relaxation times, as well as in the cross-relaxation rates between protons relaxing through fixed distances in the A ∗ residue, indicated that the molecule tumbles anisotropically in solution. However, in order to achieve agreement between the spectral and the model data, the presence of internal motions had to be also considered, in addition to the assumption of a symmetric top model for the description of overall tumbling. The changes in the longitudinal and transversal relaxation times, collected with and without suppression of interference effects, supported the assumption that the cross-correlation between dipolar and chemical shift anisotropy relaxation mechanisms cannot be neglected in this medium-sized molecule. In fact, the influence of these effects was 10–15% in T 1 and 20–25% in T 2 relaxation times. The experimental data were analyzed using model free formalism and the computed order parameters indicate a decrease in spatial restriction from the central residue ( S 2 ∼ 0.9) towards both ends of the pentasaccharide ( S 2 ∼ 0.7). The anisotropy ratio found was ∼3.3 with correlation times τ ¶ = 450 ps and τ ⊥ = 1480 ps. The values of effective correlation time were within the range of tens of picoseconds. Thus, for a more precise interpretation of the experimental data for the pentasaccharide, in addition to internal motions and anisotropic tumbling, the effect of cross-correlation must be taken into account as well.

Internal and interfacial dielectric properties of cytochrome c from molecular dynamics in aqueous solution.

The dielectric properties of proteins are central to their stability and activity. We use the Fröhlich-Kirkwood theory of dielectrics to analyze two 1-ns molecular dynamics simulations of ferro- and ferricytochrome c in spherical droplets of 1400 water molecules. Protein and solvent are idealized as a series of concentric, spherical, dielectric media. Analysis results depend strongly on the treatment of the charged protein side chains at the protein/solvent interface. If charged side chains are viewed as part of the protein medium, then the protein dipole fluctuations are dominated by large, mutually uncorrelated, anisotropic, motions of the charged side chains. It is then incorrect to view the protein region as a single, homogeneous dielectric material. If one does take this view, estimates of the protein "dielectric constant" vary from 16 to 37, depending on the exact choice of model parameters. In contrast, if the charged portions of the charged side chains are viewed as part of the solvent medium, then theory and simulation are consistent: the protein dipole fluctuations excluding charged side chains are roughly those of a homogeneous, isotropic dielectric medium, with a dielectric constant of 4.7 +/- 1.0 (ferro) or 3.4 +/- 1.0 (ferri), in agreement with powder experiments. Statistical uncertainty and sensitivity to model parameters are small. Analysis of the radial dependence of the dipole fluctuations suggests that the inner half of the protein has a somewhat lower dielectric constant of 1.5-2, consistent with its biological function in electron transfer. These results suggest that Poisson-Boltzmann models could treat the protein bulk as a low-dielectric medium and the charged surface groups as part of the solvent region.

Protein Hydration Dynamics in Aqueous Solution: A Comparison of Bovine Pancreatic Trypsin Inhibitor and Ubiquitin by Oxygen-17 Spin Relaxation Dispersion

Water oxygen-17 spin relaxation was used to study hydration and dynamcs of the globular proteins bovine pancreatic trypsin inhibitor (BPTI) and ubiquitin in aqueous solution. The frequency dispersion of the longitudinal and transverse relaxation rates was measured over the Larmor frequency range 2.6 to 49|4ru|MHz in the pD range 2 to 11 at 27°C. While the protein-induced relaxation enhancement was similar for the two proteins at high frequencies, it was an order of magnitude smaller for ubiquitin than for BPTI at low frequencies. This difference was ascribed to the absence, in ubiquitin, of highly ordered internal water molecules, which are known to be present in BPTI and in most other globular proteins. These observations demonstrate that the water relaxation dispersion in protein solutions is essentially due to a few structural water molecules buried within the protein matrix, but exchanging rapidly with the external water. The relaxation data indicate that the internal water molecules of BPTI exchange with bulk water on the time-scale 10 −8to 10 −6second thus lowering the recently reported upper bound on the residence time of these internal water molecules by four orders of magnitude, and implying that local unfolding occurs on the submircosecond time-scale The water molecules residing at the surface of the two proteins were found to be highly mobile, with an average rotational correlation time of approximately 20 picoseconds. For both proteins, the oxygen-17 relaxation depend only very weakly on pD, showing that ionic residues do not perturb hydration water dynamics more than other surface residues. We believe that the present results resolve the long-standing controversy regarding the mechanism behind the spin relaxation dispersion of water nuclei in protein solutions, thus establishing oxygen-17 relaxation as a powerful tool for studies of structurally and functionally important water molecules in proteins and other biomolecules.

Macrocyclic lanthanide DTPA-bisamides— structure and dynamics in aqueous solution.

Macrocyclic lanthanide DTPA-bisamides— structure and dynamics in aqueous solution.

Equilibria and dynamics of thallium-EDTA (Tl(edta)X2-) complexes (X = halide, pseudohalide) studied by multinuclear NMR

Equilibria and dynamics in aqueous solutions of mixed complexes Tl(edta)X[sup 2[minus]] containing ionic medium (1 M NaClO[sub 4]) have been studied by means of [sup 205]Tl-, [sup 15]N-, [sup 13]C-, and [sup 1]H-NMR and potentiometry. Individual [sup 205]Tl chemical shifts have been determined for all the investigated complexes (X = H[sub 2]O, OH, Cl, Br, CN, SCN). For the pseudohalide complexes the [sup 15]N- and [sup 13]C-NMR shifts as well as the spin-spin coupling constants J([sup 205]Tl-[sup 15]N) and J([sup 205]Tl-[sup 13]C) have also been determined. The coupling constant [sup 1]J([sup 205]Tl-[sup 13]C) for the complex Tl(edta)CN[sup 2[minus]] is remarkably large, 10 479 Hz, indicating a very strong thallium-carbon bond. The stability constants, K[sub x] = [Tl(edta)X[sup 2[minus]]]/([Tl(edta)[sup [minus]]][X[sup [minus]]]), determined by a combination of [sup 205]Tl- and [sup 13]C-NMR and potentiometry, for X = Cl, CN, and SCN are, respectively: log K[sub x] = 2.6 ([+-] = [sigma]), 8.72 ([+-] 0.03) and 2.70 ([+-] 0.03). In order to facilitate the discussion of reaction mechanisms, the crystal and molecular structure of the compound Na[sub 2][Tl(edta)CN]-3H[sub 2]O has been determined using single-crystal x-ray diffraction. This compound crystallizes in the monoclinic space group P2[sub 1]/c (no. 14) with a = 7.769 (2)more » [angstrom], b = 14.130 (6) [angstrom], c = 17.069 (5) [angstrom], [beta] = 101.44(2)[degree], and Z = 4.« less

Aggregation behavior and micellar dynamics in aqueous solutions of the nonionic surfactant pentaoxyethyleneglycol monooctyl ether: Effect of sodium halides

The aggregation behavior of pentaoxyethyleneglycol monooctyl ether (C 8E 5) in aqueous solution and some aspects of the dynamics of the C 8E 5 micelles have been investigated in the absence of added salt and in the presence of sodium halides, as a function of surfactant concentration, C (0.05 to 0.2 M), and temperature, T (2–50°C), by time-resolved fluorescence quenching. Some measurements of cloud temperature, T c , also have been performed. Both in the absence and in the presence of salt it has been found that the micelle aggregation number, N, increases slowly with T at temperatures below T c −40°C, then increases more rapidly at T> T c −40°C. The presence of salt amplifies the increase of N with T. It has been found that N is mainly determined by T c − T . Thus all N values for the 0.1 M C 8E 5 solutions in the presence of salt fall on a single curve when plotted versus T c − T , irrespective of the nature and concentration of the added salt. As for other nonionic surfactants, a rapid intermicellar migration of probe and quencher has been evidenced at T> T c − 40°C. This process has been confirmed to take place through collisions among micelles with temporary merging of the collided micelles. The rate constant K e for this process increases with T and with the concentration of added salt, that is, in both instances, upon decreasing T c − T . In the course of this work a peculiar behavior was noted when NaI was added to C 8E 5 solutions and this behavior was interpreted in terms of the formation of I 3 catalyzed by H +, in close proximity to the polyoxyethylene moieties of the surfactant micelles.