Experimental Structure Factors Research Articles

Monoclonal Antibody Aggregation near Silicone Oil-Water Interfaces.

In this work, we study the hydrodynamic behavior of monoclonal antibodies in the presence of silicone oil-water interfaces. We model the antibody molecules using a coarse-grained 24-bead model, where two beads are used to represent each antibody domain. We consider the spatial variation of the antibody polarity in our model as each bead represents a set of hydrophilic or hydrophobic amino acids. We use the dissipative particle dynamics scheme to represent the coarse-grained force field which governs the motion of the beads. In addition, interprotein interactions are modeled using an electrostatic force field. The model parameters are determined by comparing the structure factor against experimental structure factor data ranging from a low concentration regime (10 mg/mL) to a high concentration regime (150 mg/mL). Next, we conduct simulations for a suspension of antibody molecules in the presence of silicone oil-water interfaces. Protein loss from the bulk solution is noticed as the molecules adsorb at the interface. We observe dynamic cluster formation in the solution bulk and at the interface, as the antibody molecules self-associate along their trajectories. We quantify the aggregation using a density clustering algorithm and investigate the effect of the antibody concentration on the diffusivity of the antibody solution, aggregation propensity, and protein loss from the bulk. Our study shows that numerical simulations can be an important tool for understanding the molecular mechanisms driving protein aggregation near hydrophobic interfaces.

Liquid Structure and Transport Properties of the Deep Eutectic Solvent Ethaline

A range of techniques including physical property measurements, neutron scattering experiments, ab initio molecular dynamics and classical molecular dynamics simulations are used to probe the structural, thermodynamic, and transport properties of a deep eutectic solvent comprised of a 1:2 molar ratio of choline chloride and ethylene glycol. This mixture, known as Ethaline, has many desirable properties for use in a range of applications and therefore understanding its liquid structure and transport properties is of interest. Simulation results are able to capture experimental densities, diffusivities, viscosities, and structure factors extremely well. The solvation environment is dynamic and dominated by different hydrogen bonding interactions. Dynamic heterogenities resulting from hydrogen bonding interactions are quantified. Rotational dynamics of molecular dipole moments of choline and ethylene glycol are computed and found to exhibit a fast and slow mode.

Radial distribution function for liquid gallium from experimental structure factor: a Hopfield neural network approach.

Hopfield neural network was used to retrieve liquid gallium radial distribution function from an experimental structure factor, obtained at 959 K. The inversion framework was carried out under two initial conditions: (a) a constant radial distribution function corresponding to an ideal gas and (b) a step function, simulating a gas with square well potential of interaction. Both situations lead to accurate inverse results if compared with the radial distribution function obtained by Bellisent-Funel et al., using the Fourier transform method and Monte Carlo simulation. The Hopfield neural network has shown to be a powerful strategy to calculate the radial distribution function from experimental data.

Liquid Structure and Transport Properties of the Deep Eutectic Solvent Ethaline

A range of techniques including physical property measurements, neutron scattering experiments, ab initio molecular dynamics, and classical molecular dynamics simulations are used to probe the structural, thermodynamic, and transport properties of a deep eutectic solvent comprised of a 1:2 molar ratio of choline chloride and ethylene glycol. This mixture, known as Ethaline, has many desirable properties for use in a range of applications, and therefore, understanding its liquid structure and transport properties is of interest. Simulation results are able to capture experimental densities, diffusivities, viscosities, and structure factors extremely well. The solvation environment is dynamic and dominated by different hydrogen bonding interactions. Dynamic heterogeneities resulting from hydrogen bonding interactions are quantified. Rotational dynamics of molecular dipole moments of choline and ethylene glycol are computed and found to exhibit a fast and slow mode.

Ultrasonic backscattering and microstructure in sheared concentrated suspensions.

Quantitative ultrasound techniques based on the parametrization of the backscatter coefficient (BSC) are used to characterize concentrated particle suspensions. Specifically, a scattering model is fit to the measured BSC and the fit parameters can provide local suspension properties. The scattering models generally assume an isotropic microstructure (i.e., spatial organization) of the scatterers, whereas the sheared concentrated suspensions can develop an anisotropic microstructure. This paper studied the influence of the shear-induced anisotropic microstructure of concentrated suspensions on the ultrasonic backscattering. Experiments were conducted on suspensions of polymethylmetacrylate spheres (5.8 μm in radius) sheared in a Couette flow device to obtain anisotropic microstructure and then mixed by hand to obtain isotropic microstructure. Experimental structure factors that are related to the spatial distribution of sphere positions were obtained by comparing the BSCs of one concentrated and one diluted suspension. Finally, Stokesian dynamics numerical simulations of sheared concentrated suspensions are used to determine the pair correlation function, which is linked to the Fourier transform of the structure factor. The experimental structure factors are found to be in good agreement with numerical simulations. The numerical simulation demonstrates that the angular-dependent BSCs and structure factors are caused by the shear-induced anisotropic microstructure within the suspension.

Scattering from colloidal cubic silica shells: Part II, static structure factors and osmotic equation of state

HypothesisThe shape of colloidal particles affects the structure of colloidal dispersions. The effect of the cube shape on the thermodynamics of colloidal cube dispersions has not yet been studied experimentally. Static light scattering measurements on colloidal cubic silica shells at finite concentrations allows us to measure the structure factor of colloidal cube fluids and to test theoretical predictions for the equation of state of hard convex superballs. ExperimentsHollow silica nanocubes of varying concentrations in N,N,-dimethylformamide were studied with static light scattering. The structure factor was extracted from the scattering curves using experimental form factors. From this experimental structure factor, the specific density of the particles, and the osmotic compressibility were obtained. This osmotic compressibility was then compared to a theoretical equation of state of hard superballs. FindingsThe first experimental structure factors of a stable cube fluid are presented. The osmotic compressibility of the cube fluid can be described by the equation of state of a hard superball fluid, showing that silica cubes in N,N,-dimethylformamide with LiCl effectively interact as hard particles.

Structure Factor of EuCl3 Aqueous Solutions via Coupled Molecular Dynamics Simulations and Integral Equations.

Identifying the structure of an aqueous solution is essential to rationalize various phenomena such as crystallization in solution, chemical reactivity, extraction of rare earth elements, and so forth. Despite this, the efforts to describe the structure of an aqueous solution have been hindered by the difficulty to retrieve structural data both from experiments and simulations. To overcome this, first, undersaturated EuCl3 aqueous solutions of concentrations varying from 0.15 to 1.8 mol/kg were studied using X-ray scattering. Second, for the first time, the theoretical X-ray signal of 1.8 mol/kg EuCl3 aqueous solution was simulated, with precise details for the complete range of scattering vectors using coupled molecular dynamics and hypernetted chain integral equations, and satisfactorily compared with the 1.8 mol/kg experimental X-ray scattering signal. The theoretical calculations demonstrate that the experimental structure factor is dominated by Eu3+-Eu3+ correlations.

FragHAR: towards ab initio quantum-crystallographic X-ray structure refinement for polypeptides and proteins.

The first ab initio aspherical structure refinement against experimental X-ray structure factors for polypeptides and proteins using a fragmentation approach to break up the protein into residues and solvent, thereby speeding up quantum-crystallographic Hirshfeld atom refinement (HAR) calculations, is described. It it found that the geometric and atomic displacement parameters from the new fragHAR method are essentially unchanged from a HAR on the complete unfragmented system when tested on dipeptides, tripeptides and hexapeptides. The largest changes are for the parameters describing H atoms involved in hydrogen-bond interactions, but it is shown that these discrepancies can be removed by including the interacting fragments as a single larger fragment in the fragmentation scheme. Significant speed-ups are observed for the larger systems. Using this approach, it is possible to perform a highly parallelized HAR in reasonable times for large systems. The method has been implemented in the TONTO software.

Charge effects in water solution of a low generation sodium carboxylate terminated dendrimers

Dendrimers, a class of novel nano-sized materials characterized by a highly ramified structure and a relevant number of functional surface groups, represent a versatile platform for a wide range of nanotechnology applications. The number and characteristic of their modifiable surface groups strongly influence the solution properties as well as some relevant processes involved in molecular recognition, signal processing as well as for binding various targeting or guest molecules. Owing to these properties dendrimers have attracted the interest of the researchers in the development of new prototypes implicated in many technological applications. However, despite of their recent extensive studies, their colloidal stability in solution environment have been relatively less investigated. With the aim to furnish useful insight about the inter-dendrimer interaction in solution, a Small Angle X-ray Scattering (SAXS) structural investigation on the sodium carboxylate terminated (-COO-Na) generations G1.5 of poly(amidoamine) dendrimers in water solution has been performed. The presence of a pronounced interference peak in the SAXS spectra in a wide range of concentrations gives evidence of a long range electrostatic interaction which has been ascribed to the ionisation of the surface carboxylate terminal end-groups. The experimental inter-dendrimer structure factor S(q) has been analysed in the framework of liquid integral equation theory. From that, we derived an effective inter-particle interaction composed of a screened Coulombic plus hard-sphere repulsion potential, which allows the estimation of the dendrimer effective surface charge Z eff . The present analysis strongly supports the finding that colloidal stability and interaction of dendrimers in solution environment is strongly influenced by charge effects.

Structure of liquid ammonia at high pressures and temperatures

The structure of liquid ammonia (${\mathrm{NH}}_{3}$) is investigated from 1 to 6.3 GPa and up to 800 K by means of synchrotron x-ray diffraction (XRD) and ab initio molecular dynamics (AIMD) simulations. The XRD data are used to extract the molecular structure factor ${S}_{\mathrm{mol}}(Q)$, pair distribution function (PDF) ${g}_{\mathrm{mol}}(r)$, and the density of ${\mathrm{NH}}_{3}$. There is an excellent agreement between present ${S}_{\mathrm{mol}}(Q)$ and ${g}_{\mathrm{mol}}(r)$ at our lowest density and those reported in reference neutron experiments. Our densities agree better with the equation of state (EoS) of Tillner-Roth et al. [DKV-Tagungsbericht (Hannover, New York, 1993), Vol. 20, p. 167] than with more recent EoS models. The experimental structure factor and PDF are well reproduced by AIMD simulations using either the Becke-Lee-Yang-Parr or the Perdew-Burke-Ernzerhof exchange-correlation functional. The shapes of ${S}_{\mathrm{mol}}(Q)$ and ${g}_{\mathrm{mol}}(r)$ vary little over the investigated pressure range and suggest a compact liquid with weak orientational correlations between molecules, which is corroborated by the coordination number varying from 12.7 to $\ensuremath{\sim}14$. The simulations are used to study the evolution of the site-site pair distribution functions, which reveals that the number of H bonds per molecule (between 1.5 and 2) do not evolve with density and that the distribution of H atoms around N atoms becomes more and more anisotropic with pressure.

Viscoelastic effects on dynamics of concentration fluctuations in semi-dilute polymer solution in the good solvent regime

The relaxation processes of the concentration fluctuations in semi-dilute polystyrene (PS) dioctyl phthalate (DOP) solution are investigated by using dynamic light scattering (DLS) in the good solvent regime. Slow modes were found in the dynamic structure factors in the good solvent regime as found in its theta condition. They were almost independent of wavenumber, implying that the slow modes originate from the viscoelastic effects arising in dynamically asymmetric two component systems where the stress and diffusion are coupled. In order to clarify whether the viscoelastic effect indicates the slow modes, the dynamical structure factors were calculated by using Doi-Onuki (DO) theory, where the viscoelastic effects are considered in the dynamics of the concentration fluctuations of binary systems, and the calculated structure factors were compared with experimental ones. In contrast to the theta condition, the deviation was found between the calculated structure factors and experimental ones at longer time region. This deviation originates from the estimation of the osmotic compressibility from the small-angle X-ray scattering. On the other hand, interdiffusion coefficient and cooperative diffusion coefficient from calculated dynamical structure factors agree with those from experimental dynamical structure factors, indicating that both diffusion coefficients are insensitive to the relaxation process at longer time.

Ion Hydration and Association in an Aqueous Calcium Chloride Solution in the GPa Range

Neutron diffraction measurements of an aqueous 2 mol dm–3 CaCl2 solutions in D2O have been made at 1 GPa, 298 K as well as 0.1 MPa, 298 K. The experimental structure factors are subjected to Empirical Potential Structure Refinement (EPSR) modeling to reveal the ion hydration and association and solvent water at the atomic level. About seven water molecules surround Ca2+ at the Ca–O and Ca–D distances of 2.44 Å and 3.70 Å, respectively, at both pressures, suggesting no significant pressure effect on the cation hydration. On the other hand, the Cl‐ ion shows a drastic change in water oxygen coordination from ca. 7 at 0.1 MPa to ca. 14 at 1 GPa, accompanied by shortening of Cl–O distance from 3.18 Å to 3.15 Å. However, the number of water hydrogen atoms around Cl– does not change significantly as 6.0–6.7 in spite of shortening Cl–D distance from 2.22 to 2.18 Å on compression. The pressure effect on the solvent water structure is also drastic as an increase in water oxygen atoms of 4.7 at the O–O distance of 2.79 Å at 0.1 MPa to 10.3 at 2.85 Å at 1 GPa. The number of water hydrogen atoms, however, does not change as 1.2 at the O‐D distance of 1.74 Å for both pressures, demonstrating the presence of the O···D hydrogen bonds which are significantly bent at 1 GPa at 298 K. This change of hydrogen bonds in water with pressure probably causes the drastic increase in water oxygen atoms around Cl–.

Chemical Ordering in Ni66.7 In33.3 Liquid Alloy

Short range order structure of liquid Ni66,7In33,3 alloy has been studied by means of X-ray diffraction method at temperatures 1235; 1260 and 1335 K. Experimental structure factors and radial atomic distribution function are analyzed. It is shown that structure of Ni66,7In33,3 in liquid state reveals chemical ordering, like to Ni2In type structure

Molecular Dynamics Simulations of Macromolecular Crystals.

The structures of biological macromolecules would not be known to their present extent without X-ray crystallography. Most simulations of globular proteins in solution begin by surrounding the crystal structure of the monomer in a bath of water molecules, but the standard simulation employing periodic boundary conditions is already close to a crystal lattice environment. With simple protocols, the same software and molecular models can perform simulations of the crystal lattice, including all asymmetric units and solvent to fill the box. Throughout the history of molecular dynamics, studies of crystal lattices have served to investigate the quality of the underlying force fields, correlate the simulated ensembles to experimental structure factors, and extrapolate the behavior in lattices to behavior in solution. Powerful new computers are enabling molecular simulations with greater realism and statistical convergence. Meanwhile, the advent of exciting new methods in crystallography, including femtosecond free-electron lasers and image reconstruction for time-resolved crystallography on slurries of small crystals, is expanding the range of structures accessible to X-ray diffraction. We review past fusions of simulations and crystallography, then look ahead to the ways that simulations of crystal structures will enhance structural biology in the future.

Clusters of lysozyme in aqueous solutions

Equilibrium clusters of protein lysozyme are at the center of an ongoing scientific debate. Previous attempts to provide a microscopic description of the clusters that is consistent with all experimental evidence have not been fully successful. The primary reason is the use of model potentials that have a predefined shape. In this paper we derive a model-free interprotein potential directly from experimental structure factor. The derived potential is globally repulsive but has a local minimum at short distances. The minimum is essential for the correct behavior of the structure factor with protein concentration, in particular the shifting pattern of the signature maximum at short wave vectors. Equilibrium clusters are observed throughout the entire range of concentrations, but their nature differs in the low and high concentration limits. At low concentrations, the clusters are extended in shape. As the concentration is increased, small clusters collapse while large clusters are assembled from the small ones. Hydrodynamic interactions drive a kinetic slowdown at high concentrations, where a transition into a fluid of permanent clusters of specific size is observed. In good agreement with the available experimental data, our simulations shed light on the microscopic nature of protein clusters.

Tightly binding valence electron in aluminum observed through X-ray charge density study

Accurate and high reciprocal resolution experimental structure factors of aluminum were determined from a synchrotron powder X-ray diffraction data measured at 30 K with sin θ/λ < 2.31 Å−1. The structure factors have small deviations from independent atom model in sin θ/λ < 0.83 Å−1. Theoretical structure factors were prepared using density functional theoretical calculations by full potential linearized augmented plane wave method. The deviation between experimental and theoretical data was also observed at around sin θ/λ ≈ 0.4 Å−1. The charge density was determined by an extended Hansen-Coppens multipole modeling using experimental and theoretical structure factors. Charge density maxima at tetrahedral site were observed in both experimental and theoretical deformation density. The charge-density difference peaks indicating directional bonding formation were observed in the difference density between experiment and theory. The present study reveals tight binding like character of valence electron of aluminum. The fact will provide a crucial information for development of high-performance aluminum alloy.

Variations of the Hydrogen Bonding and Hydrogen-Bonded Network in Ethanol-Water Mixtures on Cooling.

Molecular dynamics computer simulations have been conducted for ethanol-water liquid mixtures in the water-rich side of the composition range, with 10, 20, and 30 mol % of alcohol, at temperatures between room temperature and the experimental freezing point of the given mixture. All-atom-type (optimized potential for liquid simulations) interatomic potentials have been assumed for ethanol, in combination with two kinds of rigid water models (SPC/E and TIP4P/2005). Both combinations have provided excellent reproductions of the experimental X-ray total structure factors at each temperature; this yielded a strong basis for further structural analyses. Beyond partial radial distribution functions, various descriptors of hydrogen-bonded assemblies, as well as of the hydrogen-bonded network have been determined. A clear tendency was observed toward that an increasing proportion of water molecules participate in hydrogen bonding with exactly two donor and two acceptor sites as temperature decreases. Concerning larger assemblies held together by hydrogen bonding, the main focus was put on the properties of cyclic entities: it was found that, similarly to methanol-water mixtures, the number of hydrogen-bonded rings has increased with lowering temperature. However, for ethanol-water mixtures, the dominance of 5-fold rings, and not 6-fold rings, could be observed.

The structure of aqueous lithium chloride solutions at high concentrations as revealed by a comparison of classical interatomic potential models

Highly concentrated aqueous lithium chloride solutions were investigated by classical molecular dynamics (MD) and reverse Monte Carlo (RMC) simulations. At first MD calculations were carried out applying twenty-nine combinations of ion-water interaction models at four salt concentrations. The structural predictions of the different models were compared, the contributions of different structural motifs to the partial pair correlation functions (PPCF) were determined. Particle configurations obtained from MD simulations were further refined using the RMC method to get better agreement with experimental X-ray and neutron diffraction data. The PPCFs calculated from MD simulations were fitted together with the experimental structure factors to construct structural models that are as consistent as possible with both the experimental results and the results of the MD simulations. The MD models were validated according to the quality of the fits. Although none of the tested MD models can describe the structure perfectly at the highest investigated concentration, their comparison made it possible to determine the main structural properties of that solution as well. It was found that four nearest neighbors (oxygen atoms and chloride ions together) are around a lithium ion at each concentration, while in the surroundings of the chloride ion hydrogen atom pairs are replaced by one lithium ion as the concentration increases. While in pure liquid water four water molecules can be found around a central water molecule, near the solubility limit nearly all water molecules are connected to two chloride ions (via their hydrogen atoms) and one lithium ion (by their oxygen atoms).

Hydration structure of reverse osmosis membranes studied via neutron scattering and atomistic molecular simulation

Reverse osmosis (RO) membranes are becoming popular as energy saving and environmentally friendly materials for the desalination of water. Toward the rational design of RO membranes, we performed contrast-variation neutron scattering measurements and atomistic molecular dynamics (MD) simulations on polyamide/water systems with various water contents and deuteration ratios. The experimental and computational structure factors showed good agreement for all the systems examined. The structure of the water-rich polyamide/water system obtained from MD calculation showed that the water clusters are well connected to each other, and a relatively large number of water molecules are present at a distance over 3 A from the polyamide. The partial radial distribution functions were calculated, and strong interactions were observed between water and the carboxyl group in polyamide. Thus, the water permeability of the RO membrane can be expected to improve when more carboxyl groups are introduced. In addition, the polyamide–polyamide interaction was found to be equal to or smaller than the polyamide–water interactions and relatively weak in the water-rich system. Reverse osmosis membranes have been playing a main role for the desalination of water in the world. Hydration structure of polyamide functional layer of the membrane was studied via neutron scattering and atomistic molecular dynamics simulations. Experimental and computational structure factors, S(Q), of the polyamide/water system showed good agreement. Water clusters in water-rich system were well connected to each other and formed channel-like structure. Polyamide–water interactions and polyamide-polyamide interactions, which are thought to be important to enhance the performance of the membranes, were examined in detail.

MO determination from experimental X-ray structure factors of diformohydrazide

MO determination from experimental X-ray structure factors of diformohydrazide