SpecDB: A relational database for archiving biomolecular NMR spectral data

Magnetic resonance spectroscopy has been used in a high-risk, high-payoff search for neuronal current (NC) signals in the free induction decay (FID) data from the visual cortex of human subjects during visual stimulation. If successful, this approach could make possible the detection of neuronal currents in the brain at high spatial and temporal resolution. Our initial experiments indicated the presence of a statistically significant change in the FID containing the NC relative to FIDs with the NC absent, and this signal was consistent with the presence of NC. Unfortunately, two follow-on experiments were not able to confirm or replicate the positive findings of the first experiment. However, even if the result from the first experiment were evidence of NC in the FID, it is clear that its effect is so small, that a true NC imaging experiment would not be possible with the current instrumentation and experimental protocol used here.

To prospectively examine whether sodium 23 (23Na) magnetic resonance (MR) imaging can be used to visualize acute intracellular Na+ accumulation and the effects of specific therapy in patients with paramyotonia congenita (PC). Ethics committee approval and informed consent were obtained. Sixteen patients (four women, 12 men; mean age, 46.7 years +/- 16.7 [standard deviation]) with confirmed PC and 10 healthy volunteers (three women, seven men; mean age, 26.6 years +/- 3) were examined by using a 1.5-T MR system with a 16.8-MHz surface coil. 23Na MR imaging was performed before and after local cooling of the nondominant lower leg and exercising, with experimentally induced weakness scored by a neurologist. The 23Na MR examination was repeated in 13 patients and all volunteers after 3 days and, additionally, in seven patients after 4 days of oral administration of mexiletine, which blocks Na+ channels. The 23Na MR protocol comprised two-dimensional (2D) fast low-angle shot (FLASH), 2D radial, and free induction decay (FID) sequences. The FID data were fitted to a biexponential decay curve to evaluate the slow and fast components of the T2 relaxation time. Fast and slow components were assigned to intra- and extracellular Na+ concentrations, respectively. Radial and FLASH MR images were evaluated by means of a region-of-interest analysis by using 0.3% saline solution for reference. T1- and T2-weighted MR imaging were also performed. Data were analyzed by using a parametric t test. After exercising, all patients developed considerable weakness exclusively in the cooled lower leg; no weakness was observed in volunteers. In patients, all 23Na MR images showed a significant increase in 23Na signal intensity in the cooled lower leg (P < .001) in comparison with nonsignificant findings in volunteers. After treatment with mexiletine, cooling and exercise induced almost no muscle weakness and no changes in 23Na MR signal intensity in patients. 23Na MR imaging enables visualization of muscular Na+ accumulation associated with muscle weakness in patients with PC, and effects of specific therapy can be detected.

Purpose:Baseline distortions in NMR spectra are caused by the corruption of the first few data points in Free Induction Decay (FID) or originated from macromolecules and lipids. To study the Singular Value Decomposition (SVD) based baseline correction method.Methods:In‐house Singular Value Decomposition (SVD) program was developed with Matlab version 7.6 (Mathworks.com). Hankel SVD method (singular value decomposition of the acquired FID signal arranged in a Hankel matrix) is used to compute the signal poles and amplitude, and from them the signal frequencies and damping factors. The estimated FID signals are constructed from the quantification parameters; residue error spectrum was calculated by FFT of the difference of original FID and estimated FID. In order to study the baseline correction effect, known simulated FID with added noise to mimic known metabolites concentration was analyzed with SVD, quantification results were compared with known reference; then baseline distortion was introduced by removing the first 5 data points, after baseline corrected with SVD method, the quantification results were compared with original reference without baseline distortion.Known patient FID acquired with Siemens Verio 3T scanner was introduced baseline distortion by removing the first 3 data points, after baseline corrected with SVD method, corrected FID were compared with original results without baseline distortion.Results:Quantification results for simulated data were compared with reference, all within 10% deviation with SNR 20.For FID acquired with Siemens Verio 3T scanner, distorted FID and calculated baseline with SVD method was compared, the baseline matches the distortion well. Corrected FID were used for quantification, the quantification results match the corrected FID well.Conclusion:As demonstrated, SVD based baseline correction method can be used to correct the FID data point missing type of distortion, results are satisfactory for both simulated data and acquired patient data.

Direct measurements of protein backbone 15N spin relaxation rates from peak line-width using a fully-relaxed Accordion 3D HNCO experiment

SQUID detected NMR in microtesla magnetic fields

Earth's Field NMR in Antarctica: A Pulsed Gradient Spin Echo NMR Study of Restricted Diffusion in Sea Ice

Paramagnetic effects are valuable structural restraints in study of structures, dynamics and interactions of proteins by means of NMR spectroscopy. Site-specific tagging of proteins with paramagnetic ions is generally required to achieve these paramagnetic effects. In this review, we first introduce the concept of paramagnetic effects including paramagnetic relaxation enhancement (PRE), pseudocontact shift (PCS) and residual dipolar couplings (RDCs), which are generally used in biomolecular NMR. Thereafter, strategies of site-specific paramagnetic tagging of proteins are outlined, and the paramagnetic effects are evaluated. On the basis of paramagnetic tagging methods described above, the applications of paramagnetic NMR in characterization of multi-domain protein replacement, 3D structural determination of unstable and low-abundance enzyme intermediate complex in real time condition, and 3D structural determination of proteins in live cells using PCSs are introduced. NMR optimized paramagnetic tags suitable for achieving high spatial resolution of distances determined by double electron-electron resonance (DEER) are reviewed. In the end, the applications of DEER measurement in characterization of protein structures in cells are demonstrated. Paramagnetic NMR and electron paramagnetic resonance (EPR) in characterization of proteins in cells is shown as a powerful technique in structural biology and chemical biology, and the development of biological compatible methods of protein modifications suitable for NMR and EPR applications are in high demand. In summary, paramagnetic tagging proteins are a powerful tool in elucidation of protein structures, dynamics and interactions in chemical and structural biology and it is surely to find wide applications in cells.

Obtaining reliable estimates of hydrogeologic properties from nuclear magnetic resonance (NMR) measurements requires the ability to measure NMR relaxation parameters that are most sensitive to pore-scale geometry. Conventional surface NMR measurements of the free induction decay yield accurate estimates of the relaxation time parameter [Formula: see text], but it has been shown that this parameter can exhibit limited sensitivity to pore size and permeability. We evaluated an improved surface-NMR scheme that uses spin-echo signals to estimate the more robust and readily usable relaxation parameter [Formula: see text]. The acquisition methodology builds upon previous spin-echo schemes and incorporates robust phase-cycling procedures, which remove responses that can potentially interfere with the echo signals. A new two-stage linear inversion was used to derive quantitative estimates of [Formula: see text] with depth. The method was evaluated in two field experiments at sites in the central and western United States. At one site, NMR logging measurements in a nearby borehole provided the first opportunity to compare [Formula: see text]-values estimated by surface NMR to [Formula: see text]-values determined from the logging data. The surface and logging results showed very close agreement at depths where [Formula: see text] is long, but echoes cannot be detected from depths where [Formula: see text] is shorter than the minimum echo time. As anticipated, we found that [Formula: see text] derived from spin echoes was generally much longer than [Formula: see text], derived from the free induction decay. We explain the observed differences by considering the magnitude of inhomogeneity in the background magnetic field. We note that [Formula: see text] exhibited greater variation and sensitivity to pore size than [Formula: see text] in coarse-grained materials, while [Formula: see text] provided greater sensitivity in fine-grained materials where no echo signal was detected. Given these complementary advantages of [Formula: see text] and [Formula: see text] measurement, we advocate adoption of a framework combining spin-echo and free induction decay data to improve characterization of groundwater aquifers.

Fast, accurate, and automatic extraction of parameters of nuclear magnetic resonance free induction decay (FID) signal for chemical spectroscopy is a challenging problem. Recently, the Steiglitz-McBride algorithm has been shown to exhibit superior performance in terms of speed, accuracy, and automation when applied to the extraction of T2 relaxation parameters for myelin water imaging of brain. Applying it to FID data reveals that it falls short of the second objective, the accuracy. Especially, it struggles with the issue of missed spectral peaks when applied to chemical samples with relatively dense frequency spectra. To overcome this issue, a preprocessing stage of subband decomposition is proposed before the application of Steiglitz-McBride algorithm to the FID signal. It is demonstrated that by doing so, a considerable improvement in accuracy is achieved. But this is not gained at the cost of the first objective, the speed. An adaptive subband decomposition is employed in conjunction with the Bayesian information criteria to carry out an efficient decomposition according to spectral content of the signal under investigation. Furthermore, adaptive subband decomposition and the Bayesian information criteria also serve to make the resulting algorithm independent of user input, which also fulfills the third objective, the automation. This makes the proposed algorithm favorable for fast, accurate, and automatic extraction of FID signal parameters.

Observation of NMR free induction decay signal in nuclear ordered solid 3He

A method of measuring the initial behavior of the free induction decay

Characterizing the variability within an ensemble of protein structures is a common requirement in structural biology and bioinformatics. With the increasing number of protein structures becoming available, there is a need for new tools capable of automating the structural comparison of large ensemble of structures. We present Protein Structural Statistics (PSS), a command-line program written in Perl for Unix-like environments, dedicated to the calculation of structural statistics for a set of proteins. PSS can perform multiple sequence alignments, structure superpositions, calculate Cartesian and dihedral coordinate statistics, and execute cluster analyses. An HTML report that contains a convenient summary of results with figures, tables, and hyperlinks can also be produced. PSS is a new tool providing an automated way to compare multiple structures. It integrates various types of structural analyses through an user-friendly and flexible interface, facilitating the access to powerful but more specialized programs. PSS is easy to modify and extend and is distributed under a free and open source license. The relevance of PSS is illustrated by examples of application to pertinent biological problems.

The major coat protein of the filamentous bacteriophage M13 is a 50-residue amphiphilic polypeptide which is inserted, as an integral membrane-spanning protein, in the inner membrane of the Escherichia coli host during infection. 13C was incorporated biosynthetically into a total of 23 of the peptide carbonyls using labeled amino acids (alanine, glycine, lysine, phenylalanine, and proline). The structure and dynamics of carbonyl-labeled M13 coat protein were monitored by 13C nuclear magnetic resonance (NMR) spectroscopy. Assignment of many resonances was achieved by using protease digestion, pH titration, or labeling of the peptide bond with both 13C and 15N. The carbonyl region of the natural-abundance 13C NMR spectrum of M13 coat protein in sodium dodecyl sulfate solution shows approximately eight backbone carbonyl resonances with line widths much narrower than the rest. Three of these more mobile residues correspond to assigned peaks (glycine-3, lysine-48, and alanine-49) in the individual amino acid spectra, and another almost certainly arises from glutamic acid-2. A ninth residue, alanine-1, also gives rise to a very narrow carbonyl resonance if the pH is well above or below the pKa of the terminal amino group. These data suggest that only about four residues at either end of the protein experience large-amplitude spatial fluctuations; the rest of the molecule is essentially rigid on the time scale of the overall rotational tumbling of the protein-detergent complex. The relative exposure of different regions of detergent-bound protein was monitored by limited digestion with proteinase K.(ABSTRACT TRUNCATED AT 250 WORDS)

High-throughput NMR structural biology can play an important role in structural genomics. We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of an homologous structure. These assignments are a prerequisite for probing protein-protein interactions, protein-ligand binding, and dynamics by NMR. Assignments are also the starting point for structure determination and refinement. A new algorithm, called Nuclear Vector Replacement (NVR) is introduced to compute assignments that optimally correlate experimentally-measured NH residual dipolar couplings (RDCs) to a given a priori whole-protein 3D structural model. The algorithm requires only uniform 15N-labelling of the protein, and processes unassigned HN-15N HSQC spectra, HN-15N RDCs, and sparse HN-HN NOE's dNNs), all of which can be acquired in a fraction of the time needed to record the traditional suite of experiments used to perform resonance assignments. NVR runs in minutes and efficiently assigns the (HN,15N) backbone resonances as well as the dNNs of the 3D \nfif-NOESY spectrum, in O(n3) time. The algorithm is demonstrated on NMR data from a 76-residue protein, human ubiquitin, matched to four structures, including one mutant (homolog), determined either by X-ray crystallography or by different NMR experiments (without RDCs). NVR achieves an average assignment accuracy of over 90%. We further demonstrate the feasibility of our algorithm for different and larger proteins, using NMR data for hen lysozyme (129 residues, 98% accuracy) and streptococcal protein G (56 residues, 95% accuracy), matched to a variety of 3D structural models. Finally, we extend NVR to a second application, 3D structural homology detection, and demonstrate that NVR is able to identify structural homologies between proteins with remote amino acid sequences using a database of structural models.

Assignment of NMR resonances of protons covalently bound to photochemically active cofactors in photosynthetic reaction centers by 13C-1H photo-CIDNP MAS-J-HMQC experiment.