Magnetic Relaxation Data Research Articles

A New Method for Determining Structure Ensemble: Application to a RNA Binding Di-Domain Protein

Structure ensemble determination is the basis of understanding the structure-function relationship of a multidomain protein with weak domain-domain interactions. Paramagnetic relaxation enhancement has been proven a powerful tool in the study of structure ensembles, but there exist a number of challenges such as spin-label flexibility, domain dynamics, and overfitting. Here we propose a new (to our knowledge) method to describe structure ensembles using a minimal number of conformers. In this method, individual domains are considered rigid; the position of each spin-label conformer and the structure of each protein conformer are defined by three and six orthogonal parameters, respectively. First, the spin-label ensemble is determined by optimizing the positions and populations of spin-label conformers against intradomain paramagnetic relaxation enhancements with a genetic algorithm. Subsequently, the protein structure ensemble is optimized using a more efficient genetic algorithm-based approach and an overfitting indicator, both of which were established in this work. The method was validated using a reference ensemble with a set of conformers whose populations and structures are known. This method was also applied to study the structure ensemble of the tandem di-domain of a poly (U) binding protein. The determined ensemble was supported by small-angle x-ray scattering and nuclear magnetic resonance relaxation data. The ensemble obtained suggests an induced fit mechanism for recognition of target RNA by the protein.

Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation

Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy.

The Nedd4-1 WW Domain Recognizes the PY Motif Peptide through Coupled Folding and Binding Equilibria.

The four WW domains of human Nedd4-1 (neuronal precursor cell expressed developmentally downregulated gene 4-1) interact with the PPxY (PY) motifs of the human epithelial Na(+) channel (hENaC) subunits, with the third WW domain (WW3*) showing the highest affinity. We have shown previously that the α-hENaC PY motif binding interface of WW3* undergoes conformational exchange on the millisecond time scale, indicating that conformational sampling plays a role in peptide recognition. To further understand this role, the structure and dynamics of hNedd4-1 WW3* were investigated. The nuclear Overhauser effect-derived structure of apo-WW3* resembles the domain in complex with the α-hENaC peptide, although particular side chain conformations change upon peptide binding, which was further investigated by molecular dynamics simulations. Model-free analysis of the (15)N nuclear magnetic resonance spin relaxation data showed that the apo and peptide-bound states of WW3* have similar backbone picosecond to nanosecond time scale dynamics. However, apo-WW3* exhibits pronounced chemical exchange on the millisecond time scale that is quenched upon peptide binding. (1)HN and (15)N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments at various temperatures revealed that apo-WW3* exists in an equilibrium between the natively folded peptide binding-competent state and a random coil-like denatured state. The thermodynamics of the folding equilibrium was determined by fitting a thermal denaturation profile monitored by circular dichroism spectroscopy in combination with the CPMG data, leading to the conclusion that the unfolded state is populated to ∼ 20% at 37 °C. These results show that the binding of the hNedd4-1 WW3* domain to α-hENaC is coupled to the folding equilibrium.

Evidence for magnetic clusters in Ni1-xVx close to the quantum critical concentration

The d-metal alloy Ni1-xVx undergoes a quantum phase transition from a ferromagnetic ground state to a paramagnetic ground state as the vanadium concentration x is increased. We present magnetization, ac-susceptibility and muon-spin relaxation data at several vanadium concentrations near the critical concentration xc ~ 11.6 % at which the onset of ferromagnetic order is suppressed to zero temperature. Below xc, the muon data reveal a broad magnetic field distribution indicative of a long-range ordered ferromagnetic state with spatial disorder. We show evidence of magnetic clusters in the ferromagnetic phase and close to the phase boundary in this disordered itinerant system as an important generic ingredient of a disordered quantum phase transition. In contrast, the temperature dependence of the magnetic susceptibility above xc is best described in terms of a magnetic quantum Griffiths phase with a power-law distribution of fluctuation rates of dynamic magnetic clusters. At the lowest temperatures, the onset of a short-range ordered cluster-glass phase is recognized by an increase in the muon depolarization in transverse fields and maxima in ac-susceptibility.

Spin Dynamics in Hybrid Iron Oxide–Gold Nanostructures

We report a broadband H-1 NMR study of the spin dynamics of coated maghemite and goldmaghemite hybrid nanostructures with two different geometries, namely dimers and coreshells. All the samples have a superparamagnetic behavior, displaying a blocking temperature (T-B similar to 80 K (maghemite), similar to 105 K (dimer), similar to 150 K (coreshell)), and the magnetization reversal time follows the VogelFulcher law. We observed three different anomalies in H-1 NMR T(1)1 versus T that decrease in amplitude when increasing the applied magnetic field. We suggest that the anomalies are related to three distinct system dynamics: molecular rotations of the organic groups (240 < T < 270 K), superparamagnetic spin blockage (100 < T < 150 K), and surfacecore spin dynamics (T < 25 K). By fitting the T(1)1 data with a heuristic model, we achieved a good agreement with magnetic relaxation data and literature values for methyl group rotation frequencies.

A histogram-based similarity measure for quantitative magnetic resonance imaging: application in acute mild traumatic brain injury.

The most commonly used summary metric in neuroimaging is the mean value, but this pays little attention to the shape of the data distribution and can therefore be insensitive to subtle changes that alter the data distribution. We propose a distributional-based metric called the normalized histogram similarity measure (HSM) for characterization of quantitative images. We applied HSM to quantitative magnetic resonance imaging T1 relaxation data of 44 patients with mild traumatic brain injury and compared with data of 43 age-matched controls. Significant differences were found between the patients and the controls in 8 gray matter regions using the HSM whereas in only 1 gray matter region based on the mean values. Our results show that HSM is more sensitive than the standard mean values in detecting brain tissue changes. Future studies on brain tissue properties using quantitative magnetic resonance imaging should consider the use of HSM to properly capture any tissue changes.

Flux dynamics and avalanches in the 122 pnictide superconductor Ba0.65Na0.35Fe2As2

In this work we present the results of the bulk magnetization measurements in a superconducting state of single crystals of Ba0.65Na0.35Fe2As2. The isothermal magnetic field (H ∥ c axis) dependent magnetization (M) loops exhibit a second peak (SP) or ‘fishtail effect’, as well as remarkable flux jumps at low temperatures. The critical current density Jc obtained from the M(H) loops is rather high, of the order of 106 A cm−2. The analysis of the temperature- and field-dependent Jc implies that high Jc is mainly due to collective (weak) pinning of vortices by dense microscopic point defects with some contribution from a strong pinning mechanism. Pronounced magnetic instabilities in terms of flux jumps depend strongly on temperature as well as on the field sweep rate. The field for the first flux jump as calculated from an adiabatic model, however, is much lower than the experimentally observed values, and this enhanced stability is attributed to a flux creep phenomenon. The analysis of field-dependent magnetic relaxation data additionally supports a collective pinning model. The data further suggest that SP in M(H) is likely related to the crossover in creep dynamics from an elastic to a plastic mechanism. We have constructed the vortex phase diagram on the field–temperature plane.

Deriving quantitative dynamics information for proteins and RNAs using ROTDIF with a graphical user interface

To facilitate rigorous analysis of molecular motions in proteins, DNA, and RNA, we present a new version of ROTDIF, a program for determining the overall rotational diffusion tensor from single- or multiple-field nuclear magnetic resonance relaxation data. We introduce four major features that expand the program's versatility and usability. The first feature is the ability to analyze, separately or together, (13)C and/or (15)N relaxation data collected at a single or multiple fields. A significant improvement in the accuracy compared to direct analysis of R2/R1 ratios, especially critical for analysis of (13)C relaxation data, is achieved by subtracting high-frequency contributions to relaxation rates. The second new feature is an improved method for computing the rotational diffusion tensor in the presence of biased errors, such as large conformational exchange contributions, that significantly enhances the accuracy of the computation. The third new feature is the integration of the domain alignment and docking module for relaxation-based structure determination of multi-domain systems. Finally, to improve accessibility to all the program features, we introduced a graphical user interface that simplifies and speeds up the analysis of the data. Written in Java, the new ROTDIF can run on virtually any computer platform. In addition, the new ROTDIF achieves an order of magnitude speedup over the previous version by implementing a more efficient deterministic minimization algorithm. We not only demonstrate the improvement in accuracy and speed of the new algorithm for synthetic and experimental (13)C and (15)N relaxation data for several proteins and nucleic acids, but also show that careful analysis required especially for characterizing RNA dynamics allowed us to uncover subtle conformational changes in RNA as a function of temperature that were opaque to previous analysis.

Structure modifications and interaction with moisture in γ-irradiated pure cellulose by thermal analysis and infrared spectroscopy

The γ-irradiation effects on cellulose structure and on its interaction with moisture were investigated. Pure cellulose paper samples were γ-irradiated in the range 0–1000 kGy. Particular attention was paid on the investigation at low absorbed doses (up to 10 kGy). Thermogravimetric analysis (TG-DTG) and Fourier Transform Infrared Spectroscopy (FTIR and ATR-FTIR) were used as complementary techniques to investigate the modifications induced by γ-irradiation on cellulose. The IR spectra confirm that the breakage of the glycosidic bonds and the formation of CO bonds are related to the oxidative degradation that is a function of the increase of the absorbed dose. At absorbed dose <10 kGy, TG-DTG data show that it is necessary to achieve higher temperature to degrade the polymeric structure. Concurrently, at the same conditions, a more stable and crystalline structure, due to cross-linking in the γ-irradiated cellulose, was correlated to the increase of the lateral crystallinity index (LCI).Aim of this work is to give a complete description of the effects induced by γ-irradiation on pure cellulose paper in a wide range of absorbed doses, with a particular attention to the modification of the cellulose–moisture interaction. A comparison between the ATR-FTIR spectra and Nuclear Magnetic Resonance Relaxation data has been reported.

Controlling magnetic properties of iron oxide nanoparticles using post-synthesis thermal treatment

Changes in morphological and magnetic properties of Fe3O4 nanoparticles before and after annealing are investigated in the present work. The nanoparticles are synthesized in a standard capacitively coupled plasma enhanced chemical vapour deposition system with two electrodes using ferrocene as the source compound. Post annealing, due to the sintering process, the particles fuse along with recrystallization. This results in increased size of the nanoparticles and the interparticle interaction, which play a major role in deciding the magnetic properties. X-ray diffraction patterns of the samples before and after annealing indicate a phase change from Fe3O4 to Fe2O3. Annealing at 200 ∘C causes the apparent saturation magnetization to increase from 6 emu g−1 to 15 emu g−1. When annealed at 500 ∘C, the magnetic properties of the nanoparticles resemble those of the bulk material. The evidence for the transition from a superparamagnetic state to a collective state is also observed when annealed at 500 ∘C. Variation of the magnetic relaxation data with annealing also reflects the change in the magnetic state brought about by the annealing. The correlation between annealing temperature and the magnetic properties can be used to obtain nanocrystallites of iron oxide with different sizes and magnetic properties.

Structural and Functional Consequences of the Cardiac Troponin C L48Q Ca2+-Sensitizing Mutation

Calcium binding to the regulatory domain of cardiac troponin C (cNTnC) causes a conformational change that exposes a hydrophobic surface to which troponin I (cTnI) binds, prompting a series of protein-protein interactions that culminate in muscle contraction. A number of cTnC variants that alter the Ca(2+) sensitivity of the thin filament have been linked to disease. Tikunova and Davis engineered a series of cNTnC mutations that altered Ca(2+) binding properties and studied the effects on the Ca(2+) sensitivity of the thin filament and contraction [Tikunova, S. B., and Davis, J. P. (2004) J. Biol. Chem. 279, 35341-35352]. One of the mutations they engineered, the L48Q variant, resulted in a pronounced increase in the cNTnC Ca(2+) binding affinity and Ca(2+) sensitivity of cardiac muscle force development. In this work, we sought structural and mechanistic explanations for the increased Ca(2+) sensitivity of contraction for the L48Q cNTnC variant, using an array of biophysical techniques. We found that the L48Q mutation enhanced binding of both Ca(2+) and cTnI to cTnC. Nuclear magnetic resonance chemical shift and relaxation data provided evidence that the cNTnC hydrophobic core is more exposed with the L48Q variant. Molecular dynamics simulations suggest that the mutation disrupts a network of crucial hydrophobic interactions so that the closed form of cNTnC is destabilized. The findings emphasize the importance of cNTnC's conformation in the regulation of contraction and suggest that mutations in cNTnC that alter myofilament Ca(2+) sensitivity can do so by modulating Ca(2+) and cTnI binding.

High-temperature change of the creep rate in YBa2Cu3O7−δfilms with different pinning landscapes

Magnetic relaxation measurements in YBa${}_{2}$Cu${}_{3}$O${}_{7\ensuremath{-}}$${}_{\ensuremath{\delta}}$ (YBCO) films at intermediate and high temperatures show that the collective vortex creep based on the elastic motion of the vortex lattice has a crossover to fast creep that significantly reduces the superconducting critical current density (${J}_{c}$). This crossover occurs at temperatures much lower than the irreversibility field line. We study the influence of different kinds of crystalline defects, such as nanorods, twin boundaries, and nanoparticles, on the high-temperature vortex phase diagram of YBCO films. We found that the magnetization relaxation data is a fundamental tool to understand the pinning at high temperatures. The results indicate that high ${J}_{c}$ values are directly associated with small creep rates. Based on the analysis of the depinning temperature in films with columnar defects, our results indicate that the size of the defects is the relevant parameter that determines thermal depinning at high temperatures. Also, the extension of the collective creep regime depends on the density of the pinning centers.

The scaling analysis on effective activation energy in HgBa2Ca2Cu3O8+δ

We review the methods of calculating the effective energy Ueff(T,B,J) for both transport measurements and magnetic decay, and suggest a new resistivity expression that is compatible with both vortex glass theory and thermal assistant flux creep theory. Then we apply these methods in our HgBa2Ca2Cu3O8+δ single phase superconductor to obtain the activation energy. Transport results confirm that the magnetic field and temperature dependence of the Ueff(T,B) can be well described by our new model. Magnetic relaxation data shows that the current density dependence of Ueff(J) can be scaled onto a single curve following the vortex glass theory. The exponent obtained from the scaling law is 0.978 in the temperature range 4.2–60 K, close to the value of 7/9 in the regime of flux creep in large vortex bundles predicted by vortex glass theory.

Time-dependent magnetization in epitaxial hard magnetic thin films

Time-dependent magnetic behaviour at room temperature is investigated in highly oriented epitaxial hard magnetic thin films. Single-layer films with nominal composition PrCo5 and PrCo7 were studied, along with two SmCo5/Fe/SmCo5 trilayer films, with Fe layer thicknesses of 11 and 16 nm. The films were prepared using pulsed laser deposition on Cr buffered MgO (110) substrates. For the trilayer system, judicious choice of the thickness of the hard (SmCo5) and soft (Fe) magnetic layers results in an exchange-coupled two-phase magnet. All the thin films exhibit switching behaviour, i.e. a near square hysteresis loop, and the details of this behaviour are explored through both measurement of the hysteresis loop, at very slow field sweep rates, and the irreversible susceptibility, χirr. Measurements of the sweep rate dependence of the intrinsic coercivity, and magnetic viscosity on the major hysteresis loop were performed. For each film, three techniques were used to determine the fluctuation field, Hf: from the sweep rate data; from the magnetization relaxation data using the waiting time method; and from S/χirr, where S is the magnetic viscosity coefficient. Differences in the value of Hf determined using the three different techniques, and the equivalence of the three techniques, are discussed. Further insights into the time-dependent behaviour of the magnetization are gained from observations of the spontaneous remagnetization, following dc demagnetization. The study shows the thin films to be of high-stability. Furthermore, it supports the view that magnetization reversal in these materials is most likely an incoherent process, and not a process involving the uniform reversal of a grain. The model of weak pinning provides a useful framework for understanding magnetization processes.

The nuclear magnetic resonance relaxation data analysis in solids: General R1/R1ρ equations and the model-free approach

The advantage of the solid state NMR for studying molecular dynamics is the capability to study slow motions without limitations: in the liquid state, if orienting media are not used, all anisotropic magnetic interactions are averaged out by fast overall Brownian tumbling of a molecule and thus investigation of slow internal conformational motions (e.g., of proteins) in solution can be conducted using only isotropic interactions. One of the main tools for obtaining amplitudes and correlation times of molecular motions in the μs time scale is measuring relaxation rate R(1)(ρ). Yet, there have been a couple of unresolved problems in the quantitative analysis of the relaxation rates. First, when the resonance offset of the spin-lock pulse is used, the spin-lock field can be oriented under an arbitrary angle in respect to B(0). Second, the spin-lock frequency can be comparable or even less than the magic angle spinning rate. Up to now, there have been no equations for R(1)(ρ) that would be applicable for any values of the spin-lock frequency, magic angle spinning rate and resonance offset of the spin-lock pulse. In this work such equations were derived for two most important relaxation mechanisms: heteronuclear dipolar coupling and chemical shift anisotropy. The validity of the equations was checked by numerical simulation of the R(1)(ρ) experiment using SPINEVOLUTION program. In addition to that, the applicability of the well-known model-free approach to the solid state NMR relaxation data analysis was considered. For the wobbling in a cone at 30° and 90° cone angles and two-site jump models, it has been demonstrated that the auto-correlation functions G(0)(t), G(1)(t), G(2)(t), corresponding to different spherical harmonics, for isotropic samples (powders, polycrystals, etc.) are practically the same regardless of the correlation time of motion. This means that the model-free approach which is widely used in liquids can be equally applied, at least assuming these two motional models, to the analysis of the solid state NMR relaxation data.

Fishtail and vortex dynamics in the Ni-doped iron pnictide BaFe1.82Ni0.18As2

We study the vortex dynamics of a ${\text{BaFe}}_{1.82}{\text{Ni}}_{0.18}{\text{As}}_{2}$ crystal with ${T}_{c}=8$ K by measuring flux creep over the second magnetization (or fishtail) peak for both $H\ensuremath{\parallel}c$ axis and $H\ensuremath{\parallel}ab$ planes. Magnetic relaxation data show an anomalously long initial stage of relaxation, lasting $\ensuremath{\sim}$10 min for the $H\ensuremath{\parallel}c$ axis and 2--3 min for $H\ensuremath{\parallel}ab$, resembling a transient effect with a lower relaxation rate, which is followed by the usual log(time) relaxation. Interestingly, study of the relaxation rate $R$ vs $H$ for both stages of relaxation and for both field directions are featureless over the field range associated with the fishtail. The same trend was confirmed by plotting $R$ vs $T$ obtained from flux-creep data measured as a function of temperature for a fixed field ($H\ensuremath{\parallel}c$ axis). A plot of the activation energy $U(M,T)$ calculated from the time of relaxation of the magnetization at a fixed field also shows a smooth behavior, further supporting the view that the fishtail peak is not associated with a crossover in a vortex pinning regime within the collective pinning scenario.

Hydrate shell models of acetate ions according to nuclear magnetic relaxation data and quantum-chemical calculations

Different ion-water clusters for the CH3COO− ion that simulate the structure of its hydrate shells in solution are considered on the basis of the quantum mechanical approach. The possible coordination of water molecules around the ion is studied and the calculation results are compared with the experimental data obtained by nuclear magnetic relaxation.

The search for negative amplitude components in quasi-continuous distributions of relaxation times: the example of 1H magnetization exchange in articular cartilage and hydrated collagen

When inverting nuclear magnetic resonance relaxation data in order to obtain quasi-continuous distributions of relaxation times for fluids in porous media, it is common practice to impose a non-negative (NN) constraint on the distributions. While this approach can be useful in reducing the effects of data distortion and/or preventing wild oscillations in the distributions, it may give misleading results in the presence of real negative amplitude components. Here, some examples of valid negative components for articular cartilage and hydrated collagen are given. Articular cartilage is a connective tissue, consisting mainly of collagen, proteoglycans and water, which can be considered, in many aspects, as a porous medium. Separate T1 relaxation data are obtained for low-mobility (‘solid’) macromolecular 1H and for higher-mobility (‘liquid’) 1H by the separation of these components in free induction decays, with α denoting the solid/liquid 1H ratio. When quasi-continuous distributions of relaxation times (T1) of the solid and liquid signal components of cartilage or collagen are computed from experimental relaxation data without imposing the usual NN constraint, valid negative peaks may appear. The features of the distributions, in particular negative peaks, and the fact that peaks at longer times for macromolecular and water protons are at essentially the same T1, are interpreted as the result of a magnetization exchange between these two spin pools. For the only-slightly-hydrated collagen samples, with α>1, the exchange leads to small negative peaks at short T1 times for the macromolecular component. However, for the cartilage, with substantial hydration or for a strongly hydrated collagen sample, both with α≪1, the behavior is reversed, with a negative peak for water at short times. The validity of a negative peak may be accepted (dismissed) by a high (low) cost of NN in error of fit. Computed distributions for simulated data using observed signal-to-noise ratios also verify the need for some negative components. Observed relaxation times and signal ratios can be fitted formally by a simple two-site exchange model that gives the exchange times and the uncoupled relaxation times of the liquid and solid components, with significant trends of these parameters with increasing 1H ratio, α. The solid-to-liquid exchange times are found to be in the range from 10 ms to a few tens of ms at all hydration levels. The results may be of interest for the application of magnetization exchange contrast in the imaging of articular cartilage to determine changes associated with pathologies and ageing. Other important porous media exist where exchange phenomena and negative relaxation components cannot be disregarded.

Fishtail effect and vortex dynamics in LiFeAs single crystals

We investigate the fishtail effect, critical current density (${J}_{c}$), and vortex dynamics in LiFeAs single crystals. The sample exhibits a second peak (SP) in the magnetization loop only with the field $||$ $c$ axis. We calculate a reasonably high ${J}_{c}$, however, values are lower than in Ba-122- and 1111-type FeAs compounds. Magnetic relaxation data imply a strong pinning which appears not to be due to conventional defects. Moreover, we find that the calculated magnetic relaxation rate is very low in LiFeAs. Our data suggest that the origin of the SP may be related to a vortex lattice phase transition. We have constructed the vortex phase diagram for LiFeAs on the field-temperature plane.

Vortex creep crossover in YBCO/PrBCO superlattices during standard magnetizationrelaxation measurements

We investigated the relaxation of the irreversible magnetization in a series of 200 nm thickYBa2Cu3O7/PrBa2Cu3O7 [(YBCO)n/(PrBCO)m] superlattices, wherethe thickness m of the nonsuperconducting PrBCO layer (measured in unit cells) was kept tom = 4 (sufficient to decouple the superconducting YBCO layers), whereas the thicknessn of the YBCO layer was varied between 2 and 20 unit cells. The analysis of standardzero-field-cooling dc magnetization relaxation data obtained in the low temperatureT region with the appliedmagnetic field H oriented along the c axis reveals the occurrence of a crossover elastic (collective) vortex creep at lowT–plastic vortexcreep at high T,generated by the T dependent macroscopic currents induced in the sample during measurements. For thin superlattices(n < 20) the creep crossover temperature , and Tcr decreaseslinearly with increasing ln(H) for a fixed n. This crossover represents an alternative to the elastic vortex glass behaviorreported for superlattices, as well as to ‘quantum vortex creep’ at unexpectedly highT inferred for thin films. We also discuss the absence of an increase of the magneticallydetermined critical current density with decreasing YBCO thickness in our superlattices,which apparently contradicts the collective pinning theories.