Fast Nuclear Magnetic Resonance Research Articles

Modern solid state NMR techniques and concepts in structural studies of synthetic polymers

In this mini-review, we present the solid state nuclear magnetic resonance (NMR) methods which trace the new tendency in structural studies of synthetic polymers. The review is organized into three sections. In the first part, short theoretical background and introduction to very fast magic angle spinning NMR technique with sample rotation 60 kHz are shown. The second part presents method for enhancing the sensitivity of NMR experiments by application of dynamic nuclear polarization magic angle spinning technique. In the third section, the power of the NMR crystallography approach which can be used for fine refinement of polymers structure on the atomic level is discussed. Copyright © 2016 John Wiley & Sons, Ltd.

Reducing acquisition times in multidimensional NMR with a time-optimized Fourier encoding algorithm.

Speeding up the acquisition of multidimensional nuclear magnetic resonance (NMR) spectra is an important topic in contemporary NMR, with central roles in high-throughput investigations and analyses of marginally stable samples. A variety of fast NMR techniques have been developed, including methods based on non-uniform sampling and Hadamard encoding, that overcome the long sampling times inherent to schemes based on fast-Fourier-transform (FFT) methods. Here, we explore the potential of an alternative fast acquisition method that leverages a priori knowledge, to tailor polychromatic pulses and customized time delays for an efficient Fourier encoding of the indirect domain of an NMR experiment. By porting the encoding of the indirect-domain to the excitation process, this strategy avoids potential artifacts associated with non-uniform sampling schemes and uses a minimum number of scans equal to the number of resonances present in the indirect dimension. An added convenience is afforded by the fact that a usual 2D FFT can be used to process the generated data. Acquisitions of 2D heteronuclear correlation NMR spectra on quinine and on the anti-inflammatory drug isobutyl propionic phenolic acid illustrate the new method's performance. This method can be readily automated to deal with complex samples such as those occurring in metabolomics, in in-cell as well as in in vivo NMR applications, where speed and temporal stability are often primary concerns.

Effects of agronomical practices on chemical composition of table grapes evaluated by NMR spectroscopy

Nutritional features of table grapes are the result of a complex combination of human practices with weather and environmental conditions. In the present study, the influence of agronomical practices on the chemical composition of commercial table grapes was studied by simple and fast nuclear magnetic resonance (NMR)-based methods. In particular, variability of grape composition was evaluated considering primary metabolites, the compounds directly involved in growth and development of fruits and reliably detected by NMR spectroscopy. Three case studies of increasing complexity were examined. Primarily, it was found that inter-vineyard composition variability has a greater discriminating effect than intra-vineyard variability. The quantities of glucose, fructose, arginine and ethanol are the most dependent on farming practices. The comparison between organic and conventional productions (cv. Superior Seedless) showed a higher sugar content for the conventional practices, resulting in a higher sugar-to-acid ratio. For cultivars Red Globe and Italia, the factors most affected by farming practices were the glucose-to-fructose ratio and the amounts of arginine and ethanol.

Ferredoxin Competes with Bacterial Frataxin in Binding to the Desulfurase IscS*

The bacterial iron-sulfur cluster (isc) operon is an essential machine that is highly conserved from bacteria to primates and responsible for iron-sulfur cluster biogenesis. Among its components are the genes for the desulfurase IscS that provides sulfur for cluster formation, and a specialized ferredoxin (Fdx) whose role is still unknown. Preliminary evidence suggests that IscS and Fdx interact but nothing is known about the binding site and the role of the interaction. Here, we have characterized the interaction using a combination of biophysical tools and mutagenesis. By modeling the Fdx·IscS complex based on experimental restraints we show that Fdx competes for the binding site of CyaY, the bacterial ortholog of frataxin and sits in a cavity close to the enzyme active site. By in vivo mutagenesis in bacteria we prove the importance of the surface of interaction for cluster formation. Our data provide the first structural insights into the role of Fdx in cluster assembly.

Advanced and Integrated Petrophysical Characterization for CO2Storage: Application to the Ketzin Site

Advanced and Integrated Petrophysical Characterization for CO<sub>2<sub/> Storage: Application to the Ketzin Site — Reservoir simulations and monitoring of CO<sub>2<sub/> storage require specific petrophysical data. We show a workflow that can be applied to saline aquifers and caprocks in order to provide the minimum data set for realistic estimations of storage potential and perform pertinent simulations of CO<sub>2<sub/> injection. The presented series of experiments are fully integrated with quantitative log data analysis to estimate porosity, irreducible saturation, drainage capillary pressure and water relative permeability, residual gas saturation, resistivity-saturation relationships and caprock transport properties (permeability and diffusivity). The case considered is a saline aquifer of the Triassic Stuttgart formation studied in the framework of the CO<sub>2<sub/>SINK onshore research storage, the first in situ testing site of CO<sub>2<sub/> injection in Germany located near the city of Ketzin.We used petrophysical methods that can provide the required data in a reasonable amount of time while still being representative of the in situ injection process. For two phase transport properties, we used the centrifuge technique. For resistivity measurements, we used the Fast Resistivity Index Measurement (FRIM) method in drainage and imbibition, at ambient and storage conditions. For caprock characterization, we used a fast NMR (Nuclear Magnetic Resonance) deuterium tracer technique to measure diffusivity and a modified steady state innovative technique to determine permeability. Entry pressure has also been evaluated using several methods. Resistivity and NMR logs were analyzed to provide a continuous estimation of irreducible saturation for the entire storage zone and to judge on the representativity of the samples analyzed in the laboratory.For the Ketzin site, the storage zone is a clayey sandstone of fluvial origin locally highly cemented, with porosity around 30% and permeability ranging from 100 to 300 mD. Two zones were identified on the logs characterized by two different irreducible saturation ranging from 15 up to 35%. The measured relative permeability curves show a sharp decrease of the water effective permeability and suggest that a saturation lower than 50% cannot be reached in practice. The exponent of the resistivity index curve is about 1.7, lower than the default value of 2. The caprock has a permeability of 27 nD, a porosity around 15% and a pore diffusivity of 0.8 x 10<sup>-9<sup/> m<sup>2<sup/>/s

Change in local dynamics of bacteriorhodopsin with retinal isomerization under pressure as studied by fast magic angle spinning NMR

Bacteriorhodopsin (bR) has a retinal with all-trans and 13-cis, 15-syn configurations whose isomeric ratio is close to 1 in the dark-adapted bR, and the population of the 13-cis, 15-syn configuration can be increased under pressure. In our previous study, we applied pressure to bR using centrifugal force introduced by sample spinning and demonstrated that the 15N nuclear magnetic resonance (NMR) signal intensity of the Schiff base in 13-cis, 15-syn retinal increased. In this study, we demonstrate a pressure-induced change in the local dynamics of the protein side in the vicinity of retinal. In the 13C dipolar decoupling and magic angle-spinning NMR spectra of [3-13C]Ala-labeled bR under fast spinning at 10 and 12 kHz, corresponding to 44 and 63 bar, respectively, the 13C NMR signal at 16.6 p.p.m. appeared prominently as a sharp peak. This peak is assigned to Ala81 and Ala84 residues located in the vicinity of the retinal. It was observed that the change in the local dynamics in the vicinity of the retinal was caused by the applied pressure. These experiments demonstrate that fast magic angle spinning in NMR provides a pressure source for investigating the structure and change in the dynamics of biomacromolecules.

High-resolution solid state NMR experiments for the characterization of calcium phosphate biomaterials and biominerals

Abstract

RelaxGUI: a new software for fast and simple NMR relaxation data analysis and calculation of ps-ns and μs motion of proteins

Investigation of protein dynamics on the ps-ns and μs-ms timeframes provides detailed insight into the mechanisms of enzymes and the binding properties of proteins. Nuclear magnetic resonance (NMR) is an excellent tool for studying protein dynamics at atomic resolution. Analysis of relaxation data using model-free analysis can be a tedious and time consuming process, which requires good knowledge of scripting procedures. The software relaxGUI was developed for fast and simple model-free analysis and is fully integrated into the software package relax. It is written in Python and uses wxPython to build the graphical user interface (GUI) for maximum performance and multi-platform use. This software allows the analysis of NMR relaxation data with ease and the generation of publication quality graphs as well as color coded images of molecular structures. The interface is designed for simple data analysis and management. The software was tested and validated against the command line version of relax.

PCS-based structure determination of protein-protein complexes.

A simple and fast nuclear magnetic resonance method for docking proteins using pseudo-contact shift (PCS) and 1HN/15N chemical shift perturbation is presented. PCS is induced by a paramagnetic lanthanide ion that is attached to a target protein using a lanthanide binding peptide tag anchored at two points. PCS provides long-range (~40 Å) distance and angular restraints between the lanthanide ion and the observed nuclei, while the 1HN/15N chemical shift perturbation data provide loose contact-surface information. The usefulness of this method was demonstrated through the structure determination of the p62 PB1-PB1 complex, which forms a front-to-back 20 kDa homo-oligomer. As p62 PB1 does not intrinsically bind metal ions, the lanthanide binding peptide tag was attached to one subunit of the dimer at two anchoring points. Each monomer was treated as a rigid body and was docked based on the backbone PCS and backbone chemical shift perturbation data. Unlike NOE-based structural determination, this method only requires resonance assignments of the backbone 1HN/15N signals and the PCS data obtained from several sets of two-dimensional 15N-heteronuclear single quantum coherence spectra, thus facilitating rapid structure determination of the protein–protein complex.Electronic supplementary materialThe online version of this article (doi:10.1007/s10858-010-9401-4) contains supplementary material, which is available to authorized users.

Does a Fast Nuclear Magnetic Resonance Spectroscopy- and X-Ray Crystallography Hybrid Approach Provide Reliable Structural Information of Ligand-Protein Complexes? A Case Study of Metalloproteinases

A human matrix metalloproteinase (MMP) hydroxamic acid inhibitor (CGS27023A) was cross-docked into 15 MMP-12, MMP-13, MMP-9, and MMP-1 cocrystal structures. The aim was to validate a fast protocol for ligand binding conformation elucidation and to probe the feasibility of using inhibitor-protein NMR contacts to dock an inhibitor into related MMP crystal structures. Such an approach avoids full NMR structure elucidation, saving both spectrometer- and analysis time. We report here that for the studied MMPs, one can obtain docking results well within 1 A compared to the corresponding reference X-ray structure, using backbone amide contacts only. From the perspective of the pharmaceutical industry, these results are relevant for the binding studies of inhibitor series to a common target and have the potential advantage of obtaining information on protein-inhibitor complexes that are difficult to crystallize.

Investigating the Locomotion of the Sandfish in Desert Sand Using NMR-Imaging

The sandfish (Scincus scincus) is a lizard having the remarkable ability to move through desert sand for significant distances. It is well adapted to living in loose sand by virtue of a combination of morphological and behavioural specializations. We investigated the bodyform of the sandfish using 3D-laserscanning and explored its locomotion in loose desert sand using fast nuclear magnetic resonance (NMR) imaging. The sandfish exhibits an in-plane meandering motion with a frequency of about 3 Hz and an amplitude of about half its body length accompanied by swimming-like (or trotting) movements of its limbs. No torsion of the body was observed, a movement required for a digging-behaviour. Simple calculations based on the Janssen model for granular material related to our findings on bodyform and locomotor behaviour render a local decompaction of the sand surrounding the moving sandfish very likely. Thus the sand locally behaves as a viscous fluid and not as a solid material. In this fluidised sand the sandfish is able to “swim” using its limbs.

Contact replacement for NMR resonance assignment

Motivation: Complementing its traditional role in structural studies of proteins, nuclear magnetic resonance (NMR) spectroscopy is playing an increasingly important role in functional studies. NMR dynamics experiments characterize motions involved in target recognition, ligand binding, etc., while NMR chemical shift perturbation experiments identify and localize protein–protein and protein–ligand interactions. The key bottleneck in these studies is to determine the backbone resonance assignment, which allows spectral peaks to be mapped to specific atoms. This article develops a novel approach to address that bottleneck, exploiting an available X-ray structure or homology model to assign the entire backbone from a set of relatively fast and cheap NMR experiments.Results: We formulate contact replacement for resonance assignment as the problem of computing correspondences between a contact graph representing the structure and an NMR graph representing the data; the NMR graph is a significantly corrupted, ambiguous version of the contact graph. We first show that by combining connectivity and amino acid type information, and exploiting the random structure of the noise, one can provably determine unique correspondences in polynomial time with high probability, even in the presence of significant noise (a constant number of noisy edges per vertex). We then detail an efficient randomized algorithm and show that, over a variety of experimental and synthetic datasets, it is robust to typical levels of structural variation (1–2 AA), noise (250–600%) and missings (10–40%). Our algorithm achieves very good overall assignment accuracy, above 80% in α-helices, 70% in β-sheets and 60% in loop regions.Availability: Our contact replacement algorithm is implemented in platform-independent Python code. The software can be freely obtained for academic use by request from the authors.Contact: gopal@cs.purdue.edu; cbk@cs.dartmouth.edu

Fast nuclear magnetic resonance correlation spectroscopy without diagonal peaks: The “2-1” correlation spectroscopy

A fast NMR experiment is proposed for measuring correlation spectroscopy (COSY) spectra with diagonal peaks completely removed or largely suppressed. This new pulse sequence is based on double quantum spectroscopy but with delayed detection, so that the double quantum coherence is effectively transferred to single quantum coherence. Therefore, the pulse sequence can be named "2-1" COSY.

A localization method for the measurement of fast relaxing13C NMR signals in humans at high magnetic fields

Nuclear magnetic resonance (NMR) signals with shortT 1 andT 2, such as the13C signal of glycogen, are difficult to localize in three dimensions without major signal loss. A pulse sequence that accomplishes the spatial localization of1H-decoupled13C NMR signals on a whole-body scanner within the Food and Drug Administration guidelines for specific absorption rates was designed. The method uses an optimized three-dimensional outer volume suppression scheme combined with one-dimensional image-selected in vivo spectroscopy and surface coil detection. The localization performance of the sequence was validated at 4 T with double chambered phantoms and13C magnetic resonance imaging. Localized13C spectra were acquired from human brain and muscle.

NMR studies of chemical structural variation of insoluble organic matter from different carbonaceous chondrite groups

Solid-state 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopic experiments have been performed on isolated meteoritic Insoluble Organic Matter (IOM) spanning four different carbonaceous chondrite meteorite groups; a CR2 (EET92042), a CI1 (Orgueil), a CM2 (Murchison), and the unique C2 meteorite, Tagish Lake. These solid state NMR experiments reveal considerable variation in bulk organic composition across the different meteorite group’s IOM. The fraction of aromatic carbon increases as CR2 < CI1 < CM2 < Tagish Lake. The increases in aromatic carbon are offset by reductions in aliphatic (sp 3) carbon moieties, e.g., “CH x,” and “CH x(O,N).” Oxidized sp 2 bonded carbon, e.g., carboxyls and ketones grouped as “CO,” are largely conservative across these meteorite groups. Single pulse (SP) 13C magic angle spinning (MAS) NMR experiments reveal the presence of nanodiamonds with an apparent concentration ranking in the IOM of CR2 < CI1 < CM2 < Tagish Lake. A pair of independent NMR experiments reveals that, on average, the aromatic moieties in the IOM of all four meteoritic IOM fractions are highly substituted. Fast spinning SP 1H MAS NMR spectral data combined with other NMR experimental data reveal that the average hydrogen content of sp 3 bonded carbon functional groups is low, requiring a high degree of aliphatic chain branching in each IOM fraction. The variation in chemistry across the meteorite groups is consistent with alteration by low temperature chemical oxidation. It is concluded that such chemistry principally affected the aliphatic moieties whereas the aromatic moieties and nanodiamonds may have been largely unaffected.

Unwarping of unidirectionally distorted EPI images.

Echo-planar imaging (EPI) is a fast nuclear magnetic resonance imaging (MRI) method. Unfortunately, local magnetic field inhomogeneities induced mainly by the subject's presence cause significant geometrical distortion, predominantly along the phase-encoding direction, which must be undone to allow for meaningful further processing. So far, this aspect has been too often neglected. In this paper, we suggest a new approach using an algorithm specifically developed for the automatic registration of distorted EPI images with corresponding anatomically correct MRI images. We model the deformation field with splines, which gives us a great deal of flexibility, while comprising the affine transform as a special case. The registration criterion is least squares. Interestingly, the complexity of its evaluation does not depend on the resolution of the control grid. The spline model gives us good accuracy thanks to its high approximation order. The short support of splines leads to a fast algorithm. A multiresolution approach yields robustness and additional speedup. The algorithm was tested on real as well as synthetic data, and the results were compared with a manual method. A wavelet-based Sobolev-type random deformation generator was developed for testing purposes. A blind test indicates that the proposed automatic method is faster, more reliable, and more precise than the manual one.

Tracer-Kinetic Analysis for Measuring Regional Cerebral Blood Flow by Dynamic Nuclear Magnetic Resonance Imaging

Measurement of regional cerebral blood flow in vivo has proved useful in the study of normal and diseased states in the brain. This circumstance has led to a variety of techniques for its quantitative determination and has continued to motivate the search for ever safer and more accurate methods of measurement. Recently, the use of nuclear magnetic resonance (NMR) in medical imaging has stimulated efforts to make it the basis for a non-invasive method of measuring flow in the brain. New advances in fast NMR imaging (MRI) provide data potentially amenable to analysis by tracer-kinetic methods.Such an analysis has not previously been available. In this paper we present theoretical results that may permit measurement of brain blood flow by NMR. The data interpreted by our model are those generated by a novel MRI protocol developed by Perman et al. (1992, Magn. Reson. Med.28, 74-83; Radiology185(P), Abstr. 154, 127) that is entirely compatible with existing routine MRI procedures. These data are fast dynamic NMR signals that reflect passage of an intravenously administered paramagnetic contrast agent serving as a plasma tracer. Our equations show how to use such data sequences to determine plasma mean transit time, plasma volume, and plasma and whole-blood flow in arbitrarily selected regions of interest in the brain. The theory accounts rigorously for recirculation of tracer to the imaged regions. Our analysis provides an explanation for the linear relationship observed experimentally by others between regional vascular volumes and time integrals of vascular-tracer residue curves, and shows that this relationship remains valid in the presence of tracer recirculation.

Cartesian echo planar hybrid scanning with two to eight echoes

A method of fast nuclear magnetic resonance (NMR) imaging which uses only square wave gradient shapes and also collects data on Cartesian coordinates in a way similar to the blipped echo planar imaging method (BEPI) is described. The method is a heuristic attempt at finding an optimal data collection strategy for NMR imaging. Its advantages and disadvantages compared to other methods are carefully analyzed. Clinical size anatomical (head and body) images are shown. It is found that the interecho phase-angle discrepancies that are caused bv the B(0) inhomogeneity and by the gradient wave form distortion can largely be eliminated by using the half Fourier method with full Fourier phase map correction, but one phase map is required for each echo. GRASS/FLASH spoiling techniques are incorporated into the method in order to allow multiecho speed increases for scans which would run under 10 s using a single-echo method. The technique can be applied directly to GRASS/FLASH itself, as is demonstrated by a two-echo GRASS scan. The fastest image was 1.9 s.

Fast NMR Imaging by Concentric Sampling

The generation of multiple spin echoes by means of rapid gradient reversal has proved to be a pronising approach for speeding up the data acquisition time in nuclear magnetic resonance (NMR) imaging. In this paper, we apply the oscillating gradient technique to the line integral projection reconstruction (LIPR) method for two dimensional imaging. Ihe current approach differs from the LIPR method in that the free induction decay (FID) signal is sampled around concentric circles instead of along radial lines as is the case with the LIPR method. The proposed technique combines the advantages of echo planar imaging (EPI) and the LIPR method and provides high speed artifact free images. Simulation results using the new method are presented. Various practical considerations are discussed.