Molecular dynamics of glucose in solution: a quasielastic neutron scattering study

The molecular dynamics of glucose dissolved in heavy water have been investigated at 280 K by the technique of quasielastic neutron scattering. The scattering was described by a dynamic structure factor that accounts for decoupled diffusive jumps and free rotational motions of the glucose molecules. With increasing glucose concentration, the diffusion constant decreases by a factor five and the time between jumps increases considerably. Our observations validate theoretical predictions concerning the impact of concentration on the environment of a glucose molecule and the formation of cages made by neighboring glucose molecules at higher concentrations.     

Origin of repulsive force and structure/dynamics of interfacial water in OEG-protein interactions: a molecular simulation study

Molecular simulations were performed to investigate the origin of the strong repulsive force acting on a protein as the protein approaches an oligo (ethylene glycol) self-assembled monolayer (OEG-SAM) surface. Since the repulsive force is mainly generated from water molecules, the force from the water molecules near the surface was calculated layer by layer to further identify the molecular origin of the repulsive force. Results show that the strong repulsive force acting on the protein near the OEG-SAM surface is dominantly generated by the interfacial water molecules located between the OEG-SAM surface and lysozyme. A hydroxyl-terminated SAM (OH-SAM) surface was used for comparison. No significant repulsive force was observed from the water molecules between the protein and OH-SAM surface. Further studies show that the dipole distribution of the interfacial water molecules is significantly affected by the OEG-SAM surface, as opposed to the negligible impact from the OH-SAM surface. The interfacial water molecules above the OEG-SAM surface stay longer and reorient more slowly than those above the OH-SAM surface. These results from this work support the hypothesis that the OEG-SAM surface interacts strongly with interfacial water molecules and creates a stable hydration layer that prevents proteins from adsorbing to the surface.     

Influence of hydration on protein dynamics: combining dielectric and neutron scattering spectroscopy data

Combining dielectric spectroscopy and neutron scattering data for hydrated lysozyme powders, we were able to identify several relaxation processes and follow protein dynamics at different hydration levels over a broad frequency and temperature range. We ascribe the main dielectric process to protein's structural relaxation coupled to hydration water and the slowest dielectric process to a larger scale protein's motions. Both relaxations exhibit a smooth, slightly super-Arrhenius temperature dependence between 300 and 180 K. The temperature dependence of the slowest process follows the main dielectric relaxation, emphasizing that the same friction mechanism might control both processes. No signs of a proposed sharp fragile-to-strong crossover at T approximately 220 K are observed in temperature dependences of these processes. Both processes show strong dependence on hydration: the main dielectric process slows down by six orders with a decrease in hydration from h approximately 0.37 (grams of water per grams of protein) to h approximately 0.05. The slowest process shows even stronger dependence on hydration. The third (fastest) dielectric relaxation process has been detected only in samples with high hydration ( h approximately 0.3 and higher). We ascribe it to a secondary relaxation of hydration water. The mechanism of the protein dynamic transition and a general picture of the protein dynamics are discussed.     

Molecular dynamics of n-hexane: a quasi-elastic neutron scattering study on the bulk and spatially nanochannel-confined liquid

We present incoherent quasi-elastic neutron scattering measurements in a wave vector transfer range from 0.4 A?(-1) to 1.6A? (-1) on liquid n-hexane confined in cylindrical, parallel-aligned nanochannels of 6 nm mean diameter and 260 μm length in monolithic, mesoporous silicon. They are complemented with, and compared to, measurements on the bulk system in a temperature range from 50 K to 250 K. The time-of-flight spectra of the bulk liquid (BL) can be modeled by microscopic translational as well as fast localized rotational, thermally excited, stochastic motions of the molecules. In the nano-confined state of the liquid, which was prepared by vapor condensation, we find two molecular populations with distinct dynamics, a fraction which is immobile on the time scale of 1 ps to 100 ps probed in our experiments and a second component with a self-diffusion dynamics slightly slower than observed for the bulk liquid. No hints of an anisotropy of the translational diffusion with regard to the orientation of the channels' long axes have been found. The immobile fraction amounts to about 5% at 250 K, gradually increases upon cooling and exhibits an abrupt increase at 160 K (20 K below bulk crystallization), which indicates pore freezing.     

Preferential hydration of lysozyme in water/glycerol mixtures: a small-angle neutron scattering study

In solution small-angle neutron scattering has been used to study the solvation properties of lysozyme dissolved in water/glycerol mixtures. To detect the characteristics of the protein-solvent interface, 35 different experimental conditions (i.e., protein concentration, water/glycerol fraction in the solvent, content of deuterated compounds) have been considered and a suitable software has been developed to fit simultaneously the whole set of scattering data. The average composition of the solvent in the close vicinity of the protein surface at each experimental condition has been derived. In all the investigated conditions, glycerol resulted especially excluded from the protein surface, confirming that lysozyme is preferentially hydrated. By considering a thermodynamic hydration model based on an equilibrium exchange between water and glycerol from the solvation layer to the bulk, the preferential binding coefficient and the excess solvation number have been estimated. Results were compared with data previously derived for ribonuclease A in the same mixed solvent: even if the investigated solvent compositions were very different, the agreement between data is noticeable, suggesting that a unique mechanism presides over the preferential hydration process. Moreover, the curve describing the excess solvation number as a function of the solvent composition shows the occurrence of a region of maximal hydration, which probably accounts for the changes in protein stability detected in the presence of cosolvents.     

Small-angle neutron scattering study of microemulsion-polymer mixtures in the protein limit

Contrast variation small-angle neutron scattering (SANS) has been employed to study complex fluids comprising model microemulsions and polymers. The systems are water-in-oil microemulsions with added non-adsorbing polymer, under good polymer solvency conditions and semidilute polymer concentrations. The polymer/colloid size ratio was q approximately 11, which is well within the "protein limit". Four scattering contrasts were produced by selective deuteration of the dispersed and continuous phases and also the surfactant. In this way, the separate partial structure factors (PSF) for colloid-colloid (c-c), polymer-polymer (p-p), and colloid-polymer (c-p) have been obtained. The c-c PSF has been compared with theoretical predictions, allowing determination of a polymer correlation length. This is compared with a similar correlation length obtained from the p-p PSF, which is shown to increase with colloid concentration. In this sense, adding microemulsion has a similar effect on the dissolved polymer as reducing the solvent quality, and an effective Flory-Huggins chi parameter has been calculated. The cross-term PSF shows a distinct anti-correlation. This is the first time such structure factors have been determined experimentally for colloid-polymer systems in the protein limit and these allow a more detailed understanding of the structural interactions in these systems.     

The driving force for co-translational protein folding is weaker in the ribosome vestibule due to greater water ordering

Interactions between the ribosome and nascent chain can destabilize folded domains in the ribosome exit tunnel''s vestibule, the last 3 nm of the exit tunnel where tertiary folding can occur. Here, we test if a contribution to this destabilization is a weakening of hydrophobic association, the driving force for protein folding. Using all-atom molecular dynamics simulations, we calculate the potential-of-mean force between two methane molecules along the center line of the ribosome exit tunnel and in bulk solution. Associated methanes, we find, are half as stable in the ribosome''s vestibule as compared to bulk solution, demonstrating that the hydrophobic effect is weakened by the presence of the ribosome. This decreased stability arises from a decrease in the amount of water entropy gained upon the association of the methanes. And this decreased entropy gain originates from water molecules being more ordered in the vestibule as compared to bulk solution. Therefore, the hydrophobic effect is weaker in the vestibule because waters released from the first solvation shell of methanes upon association do not gain as much entropy in the vestibule as they do upon release in bulk solution. These findings mean that nascent proteins pass through a ribosome vestibule environment that can destabilize folded structures, which has the potential to influence co-translational protein folding pathways, energetics, and kinetics.

In the ribosome vestibule, the contact minimum between two methane molecules is half as stable as compared to in bulk solution, demonstrating that the hydrophobic effect is weakened in the vestibule of ribosome exit tunnel.     

Small-angle neutron scattering on a core-shell colloidal system: a contrast-variation study

Small-angle neutron scattering (SANS) measurements are reported on a sterically stabilized, core-shell colloidal system using contrast variation. Aqueous dispersions of polystyrene particles bearing grafted poly(ethylene glycol) (PEG) have been studied over a large range of particle concentrations and two different solvent conditions for the PEG polymer. SANS data are analyzed quantitatively by modeling the particles as core-shell colloids. In a good solvent and under particle contrast conditions, an effective hard-sphere interaction captures excluded-volume interactions up to high concentrations. Contrast variation, through isotopic substitution of both the core and solvent, expedite a detailed study of the PEG layer, both in the dilute limit and as a function of the particle concentration. Upon diminishing the solvent quality, subtle changes in the PEG layer translate into attractions among particles of moderate magnitude.     

Molecular dynamics and neutron scattering study of the dependence of polyelectrolyte dendrimer conformation on counterion behavior

Atomistic molecular dynamics (MD) simulations and contrast variation small angle neutron scattering (SANS) have been combined to investigate the Generation-5 polyelectrolyte polyamidoamine starburst dendrimer. This work reveals the dendrimer conformational dependence on counterion association at different levels of molecular charge. The accuracy of the simulations is verified through satisfactory comparison between modeled results, such as excess intra-dendrimer scattering length density distribution and hydration level, and their experimental counterparts. While the counterion distributions are not directly measureable with SANS, the spatial distribution of the counterions and their dendrimer association are extracted from the validated MD equilibrium trajectories. It is found that the conformation of the charged dendrimer is strongly dependent on the counterion association. Sensitivity of the distribution of counterions around charged amines to the counterion valency is qualitatively explained by adopting Langmuir adsorption theory. Moreover, via extending the concept of electrical double layer for compact charged colloids, we define an effective radius of a charged dendrimer including the spatial distribution of counterions in its vicinity. Within the same framework, the correlation between the strength of intra-dendrimer electrostatic repulsion and the counterion valency and dynamics is also addressed.     

nMoldyn: a program package for a neutron scattering oriented analysis of molecular dynamics simulations

We present a new implementation of the program nMoldyn, which has been developed for the computation and decomposition of neutron scattering intensities from Molecular Dynamics trajectories (Comp. Phys. Commun 1995, 91, 191-214). The new implementation extends the functionality of the original version, provides a much more convenient user interface (both graphical/interactive and batch), and can be used as a tool set for implementing new analysis modules. This was made possible by the use of a high-level language, Python, and of modern object-oriented programming techniques. The quantities that can be calculated by nMoldyn are the mean-square displacement, the velocity autocorrelation function as well as its Fourier transform (the density of states) and its memory function, the angular velocity autocorrelation function and its Fourier transform, the reorientational correlation function, and several functions specific to neutron scattering: the coherent and incoherent intermediate scattering functions with their Fourier transforms, the memory function of the coherent scattering function, and the elastic incoherent structure factor. The possibility to compute memory function is a new and powerful feature that allows to relate simulation results to theoretical studies.     

Hydrogen dynamics in Na3AlH6: a combined density functional theory and quasielastic neutron scattering study

Understanding the elusive catalytic role of titanium-based additives on the reversible hydrogenation of complex hydrides is an essential step toward developing hydrogen storage materials for the transport sector. Improved bulk diffusion of hydrogen is one of the proposed effects of doping sodium alanate with TiCl3, and here we study hydrogen dynamics in doped and undoped Na3AlH6 using a combination of density functional theory calculations and quasielastic neutron scattering. The hydrogen dynamics is found to be vacancy mediated and dominated by localized jump events, whereas long-range bulk diffusion requires significant activation. The fraction of mobile hydrogen is found to be small for both undoped and doped Na3AlH6, even at 350 K, and improved hydrogen diffusion as a result of bulk-substituted titanium is found to be unlikely. We also propose that previously detected low-temperature point defect motion in sodium alanate could result from vacancy-mediated sodium diffusion.     

Amphiphilic networks based on cross-linked star polymers: a small-angle neutron scattering study

Four different polymer model networks of identical molecular architecture based on cross-linked stars (CLSs) were investigated by small-angle neutron scattering (SANS). One of the model networks was a hydrophilic homopolymer CLS of 2-(dimethylamino)ethyl methacrylate (DMAEMA), and the other three were amphiphilic copolymer CLS co-networks of DMAEMA and hydrophobic methyl methacrylate (MMA): one based on a star with random copolymer arms and the other two based on heteroarm star copolymers. For the homopolymer and random copolymer star networks, the scattering curves show shoulders at low values of the scattering vector, indicating very small compacted domains with radii of 1.0-1.3 nm, with the random copolymer star co-network having somewhat larger domains. For the heteroarm star co-networks, pronounced peak maxima are observed because of a much higher degree of microphase structuring than for the other two co-networks. The scattering patterns are described by the presence of well-defined hydrophobic domains with radii of 7.1 and 10.3 nm in the two heteroarm star co-networks, respectively, thereby proving pronounced microphase separation in these systems.     

A small angle neutron scattering study of the sodium di-n-pentyl phosphate micelles in water

Small angle neutron scattering has been used to elucidate the size and shape of a micelle in the sodium di-n-pentyl phosphate (DPP)-water system. The results are summarized as follows. For the DPP micelle, the aggregation number (n) depends on the concentration (n=12, at 7.0 wt% andn=15 at 10.0 wt%). The minimum micelle is spherical and has an aggregation numbern=7. For the DPP-micellar system, it can be assumed that micellar growth and variation from the spherical to probate shape occurs with an increase in concentration above the CMC.     

Hydrogen motions in the alpha-relaxation regime of poly(vinyl ethylene): a molecular dynamics simulation and neutron scattering study

The hydrogen motion in poly(vinyl ethylene) (1,2-polybutadiene) in the alpha-relaxation regime has been studied by combining neutron spin echo (NSE) measurements on a fully protonated sample and fully atomistic molecular dynamics simulations. The almost perfect agreement between experiment and simulation results validates the simulated cell. A crossover from Gaussian to non-Gaussian behavior is observed for the intermediate scattering function obtained from both NSE measurements and simulations. This crossover takes place at unusually low Q values, well below the first maximum of the static structure factor. Such anomalous deviation from Gaussian behavior can be explained by the intrinsic dynamic heterogeneity arising from the differences in the dynamics of the different protons in this system. Side group hydrogens show a markedly higher mobility than main chain protons. Taking advantage of the simulations we have investigated the dynamic features of all different types of hydrogens in the sample. Considering each kind of proton in an isolated way, deviations from Gaussian behavior are also found. These can be rationalized in the framework of a simple picture based on the existence of a distribution of discrete jumps underlying the atomic motions in the alpha process.     

Proline-based chiral stationary phases: a molecular dynamics study of the interfacial structure

Proline chains have generated considerable interest as a possible basis for new selectors in chiral chromatography. In this article, we employ molecular dynamics simulations to examine the interfacial structure of two diproline chiral selectors, one with a terminal trimethylacetyl group and one with a terminal t-butyl carbamate group. The solvents consist of a relatively apolar n-hexane/2-propanol and a polar water/methanol mixture. We begin with electronic structure calculations for the two chiral selectors to assess the energetics of conformational changes, particularly along the backbone where the amide bonds can alternate between cis and trans conformations. Force fields have been developed for the two selectors, based on these ab initio calculations. Molecular dynamics simulations of the selective interfaces are performed to examine the preferred backbone conformations, as a function of end-group and solvent. The full chiral surface includes the diproline selectors, trimethylsilyl end-caps, and silanol groups. Connection is made with selectivity measurements on these interfaces, where significant differences are observed between these two very similar selectors.     

Small-angle neutron scattering study on the transamidition of polyamide-4.6

The interchange or so-called transamidation process in polyamide-4.6 was investigated by means of small-angle neutron scattering (SANS). For this purpose, a 50/50 blend of partially deuterated and fully hydrogenous polyamide-4.6 was processed at 300°C for variable times (1–20 min). The obtained results are in line with the theory as described by Benoit to quantify the transesterfication process in homopolyesters. An exponential relaxation time τ of approximately 1500 s was obtained. On the basis of this relaxation time τ, it can be calculated that approximately four interchange reactions per chain occur in polyamide-4.6 during a typical processing time of 3 min at 300°C. The data interpretation is not complicated by the presence of some crystallinity in polyamide-4.6. © 1996 John Wiley & Sons, Inc.     

A neutron scattering study of the structure and water partitioning of selectively deuterated copolymer micelles

We present a scattering study of a selectively deuterated micelle-forming diblock copolymer. The copolymer comprises a partially deuterated polystyrene (d,h-PS) block and an imidazolium-functionalized PS (IL) block. In toluene solutions, the copolymers assemble into elongated micelles where the IL block forms the micelle core. Through dynamic light scattering (DLS) measurements, we obtain the overall size of the micelles. In our small-angle neutron scattering (SANS) studies, we use contrast matching to characterize the IL core and the PS shell of the micelles independently. The PS block forming the micelle shell exhibits either a starlike or brushlike conformation depending upon the size of the core to which it is tethered. We find the IL block to be in an extended conformation, driving the formation of slightly elongated and relatively stiff micelle cores. The elongated micelle core cross-sectional radius and length depend linearly on the length of the IL block. We find that the micelles can sequester a few water molecules for each IL repeat unit; the addition of water slightly increases the cross section of the elongated micelles.     

Adsorption of beta-hairpin peptides on the surface of water: a neutron reflection study

Neutron reflectivity has been used to determine the thickness and surface coverage of monolayers of two 14-residue beta-hairpin peptides adsorbed at the air/water interface. The peptides differed only in that one was labeled with a fluorophore, while the other was not. The neutron reflection measurements were mainly made in null reflecting water, NRW, containing 8.1% D(2)O. Under this isotopic contrast the water is invisible to neutrons and the specular signal was then only from the peptide layer. At the highest concentration of ca. 4 microg/mL studied, the area per peptide molecule (A) was found to be 230 +/- 10 and 210 +/- 10 A(2) for the peptides with and without a BODIPY-based fluorophore, respectively. The thickness of the peptide layers was about 10 A for a Gaussian distribution. With decreasing bulk peptide concentration, both surface excess and layer thickness showed a steady trend of decrease. While the neutron results clearly indicate structural changes within the peptide monolayers with increasing bulk concentration, the outstanding structural feature is the formation of rather uniform peptide layers, consistent with the structural characteristics typical of beta-strand peptide conformations. These structural features are well supported by the parallel measurements of the adsorbed layers in D(2)O. With this isotopic contrast the neutron reflectivity provides an estimate about the extent of immersion of the peptide layers into water. The results strongly suggest that the 14-mer peptide monolayers were fully afloat on the surface of water, with only the carboxy groups on Glu residues hydrated.     

Hydrogen in N-methylacetamide: positions and dynamics of the hydrogen atoms using neutron scattering

This work reports neutron diffraction and incoherent neutron scattering experiments on N-methylacetamide (NMA), which can be considered the model building block for the peptide linkage of polypeptides and proteins. Using the neutron data, we have been able to associate the onset of a striking negative thermal expansion (NTE) along the a-axis with a dynamical transition around 230 K, consistent with our calorimetric experiments. Observation of the NTE raises the question of possible proton transfer in NMA, which, from our data alone, still cannot be settled. We can only speculate that intermolecular repulsive forces increase as the O...H distance decreases upon cooling, and that around 230 K the lattice relaxes without observation of an actual proton transfer. However, the existence of a nonharmonic potential, reflected by the behavior of the phonon vibrations together with the observation of NTE, could be justified by the "vibrational" polaron theory in which a dynamic localization of the vibrational energy is created by coupling an internal molecular mode to a lattice phonon. More generally, this work shows that neutron powder diffraction techniques can be very powerful for investigating structural deformations in small peptide systems.     

A small-angle neutron scattering study of the ethyl (n-octyl) phosphate micelles in water

Summary Mixed-double chain anionic surfactants, barium- and lithium-salts of ethyl(n-octyl) phosphate (EOP), which are asymmetric in the molecular shape, and a series of identical chain di-n-alkyl phosphate lithium salts have been synthezized. The limiting partial molar volume of a PO ₄ ^– group (23.43±0.41 cm³ mol^–1) for use in small-angle neutron scattering analysis was determined by density measurements of a series of identical chain di-n-alkyl phosphate lithium salts. For lithium EOP-D₂O system, a critical micellar concentration (2.3 wt%) was determined by³¹P NMR spectra. The micellar shape and size in the EOP-water binary system has been investigated by using small-angle neutron scattering (SANS) spectra. It has been found that the micelles of barium EOP in water have the shape of a prolate spheroid and aggregation numbers (n) equal to 48 at 23°C and 52 at 50°C. For the lithium EOP-micellar system, it has been found that the minimum micelle with an aggregation numbern=21 is spherical and micellar growth and variation from the spherical to the prolate shape might occur with an increase in concen tration above the CMC.