Preprints  

There is growing interest in mapping exchange dynamics between Watson-Crick and Hoogsteen conformations across different DNA contexts. However, current methods are ill-suited for measurements at a large scale because they require isotopically enriched samples. We report that Hoogsteen dynamics can be measured on unlabeled samples using ¹H CEST experiments, which have higher throughput and lower cost relative to conventional methods and also provide new insights into Hoogsteen dynamics.

To increase experimental efficiency, information can be encoded in parallel by taking advantage of highly resolved NMR spectra. Here we demonstrate parallel encoding of optimal diffusion parameters by selectively using a resonance for each molecule in the sample. This yields a factor of n decrease in experimental time since n experiments can be encoded into a single measurement. This principle can be extended to additional experimental parameters as a means to further improve measurement time.

Quantum-rotor induced polarization, also called the "Haupt effect" is a hyperpolarization technique in NMR relying on the couplings of nuclear spin-states to rotational quantum states. The classical molecule showing this effect is gamma-picoline. One might assume that many other molecules carrying a methyl group might also show the effect. Here we explore in a heuristical approach other molecules which appear to be promising candidates.

The signals that are attainable in conventional NMR are tiny and consequentially, NMR is often a slow and insensitive. The intensity may be increased by hyperpolarization, provided that the spectral quality is essentially preserved. We have recently reported a potentially powerful hyperpolarization scheme, named bullet-DNP. Here, we report a 10-fold improvement in resolution for that method, which may enable new applications in metabolomics and drug discovery.

Fluorine NMR was used to study the interaction between a proline-rich peptide and a SH3 domain using 4S- and 4R fluorinated prolines whose potential as NMR probes has not been exploited yet. We present a comprehensive study addressing several aspects to be considered when using these residues as NMR probes, including relaxation and dynamics. We show that their conformational bias may be used to modulate the kinetics of protein binding to proline-rich motifs.

We provide a proof of concept that relaxation and diffusion parameters can be determined from nuclear spin noise spectra acquired with customizable sequences of switched magnetic field gradients. The methods do not require any excitation with a radio frequency source.

The Biological Magnetic Resonance Data Bank (BMRB) has been used to identify overall trends, for example the relationship between chemical shift and backbone conformation. The BMRB archive has grown so that statistical outliers are sufficiently numerous to afford insights into unusual or unique structural features in proteins. We analyze amide proton chemical shift outliers to gain insights into the occurence of hydrogen bonds between an amide NH and the p-pi cloud of aromatic side-chains.

Diffusion-ordered spectroscopy (DOSY) seeks to distinguish between the NMR signals of chemical species of different sizes, using experimental measurements of spectra with different diffusion weighting. This paper examines how the signal-to-noise ratio of the experimental data influences the ability to distinguish small differences in diffusion coefficient between species.

The HSQC experiment developed by Bodenhausen and Ruben is a cornerstone for modern NMR. When used in the field of metabolomics, the common practice of decoupling in the proton dimension limits the acquisition time and hence the resolution. Here, we present a virtual decoupling method to maintain both spectral simplicity and resolution, and demonstrate how it increases information content with the Zebra mussel metabolome as an example.

The original theories of NMR relaxation Felix Bloch are exposed and explicated, thereby connecting these marginalized, but important scientific papers with the new modern approaches.

Novel electron spin resonance (ESR) detectors based on voltage-controlled oscillators (VCOs) have been gaining attention, mainly due to the possibility of integrating the whole ESR spectrometer onto a single printed circuit board at relatively low cost, while maintaining a performance comparable to commercial solutions. We present an experimental setup where the signal is detected as a change in VCO oscillation amplitude, along with in-depth theoretical analysis of the novel readout scheme.

Electron paramagnetic resonance (EPR) spectroscopy is the method of choice to investigate and quantify paramagnetic species. We present the application of an unconventional EPR detection method, rapid scan EPR, to enhance the sensitivity on an improved design of a miniaturized EPR spectrometer implemented on a silicon microchip. Due to its size, it may be integrated into complex and harsh sample environments enabling in situ or operando EPR measurements that have previously been inaccessible.

We use the theory of magnetostatic reciprocity to compute manufacturable solutions of complex magnet geometries, establishing a quantitative metric for the placement and subsequent orientation of discrete pieces of permanent magnetic material. This leads to self-assembled micro magnets, adjustable magnetic arrays, and an unbounded magnetic field intensity in a small volume, despite realistic modelling complex material behaviours.

Providing evidence that proteins are dynamical molecules is a major contribution of solution NMR to structural biology. But the classical experiments to measure dynamics can only be applied to small proteins. This is regretful, because larger proteins often display conformational changes in which dynamics plays a functional role. We show here that dynamic information can be extracted from HSQC NMR spectra using a computational approach. Such spectra are widely available also for larger proteins.

We develop an exact analytical description of spinning sideband intensities in magic-angle spinning NMR, e.g. for ¹³C CSA. This can be used in spectral fitting to obtain tensor parameters, and plays out its advantage in the analysis of orientation effects in non-isotropic samples. We present an improved approach to process data obtained with the simple “syncMAS” experiment, which is powerful but not very popular due to the so far not very transparent and difficult data analysis.

Kidney stones (KS) are a major health problem in industrialized countries. The study of KS is presently at the heart of a concerted multi-disciplinary axis of research involving physicians, physical chemists and spectroscopists. In this contribution, an in-depth structural description of kidney stones is proposed by implementing a combination of multinuclear and multidimensional solid state NMR methodology.

Long-lived nuclear spin order overcomes the limited timescale of polarization storage by displaying much longer lifetimes compared to the longitudinal and transversal magnetizations. However, the excitation of these symmetry-adapted states required spin choreographies that were often overshadowed by their applications. Here, we recapitulate some of the milestones achieved in designing suited pulse sequences and comment on some future perspectives.

A straightforward lineshape analysis of the ¹³C spectral asymmetries of [2-¹³C]sodium acetate can be used to indirectly evaluate the ¹H polarization of the CH₃ group, and likely entire samples in the case of rapid and homogeneous ¹H-¹H spin diffusion. The results are potentially advantageous for polarizers that lack ¹H radiofrequency hardware, measurements which are influenced by radiation damping or large background signals, or where acquisition of thermal equilibrium spectra are not feasible.

The overall aim of the study is to provide a basis from which to improve the ability of tamoxifen family drugs to reduce the activity of a secondary target protein, calmodulin, during tumour development. The main conclusion is that the binding of a tamoxifen analogue is quite unlike that of other anti-calmodulin compounds, in that two drug molecules bring the two domains of calmodulin into close proximity, but they are not fixed in orientation relative to the protein.

We show here that information about protein molecular dynamics can be directly extracted out of a single NMR spectrum. Understanding protein dynamics is essential to understanding its function, energetics and biology. We hope that this contribution helps bring this insight to a much broader application field and audience community than previously possible.

The demonstration of the Finite Pulse Radio Frequency Driven Recoupling experiment was firstly published over the past 20 years. Since it has become one of the used experiments. In this article we consider that experiment using other theoretical and simulated approaches with respect to the previous works. These approaches help us to understand more clearly the influence of each part of that experiment and to see how exactly the spin system is evaluated during it.

We recently added 2D NMR spectroscopy to the well-established techniques able to obtain information on the process of unfolding using resonances of residues in the hydrophobic core of a protein. We asked whether a detailed analysis of the individual stability curves could provide additional site-specific information. By monitoring both cold and heat denaturation of individual residues we convincingly demonstrate that the two unfolding processes are intrinsically different.

Nowadays, almost all MRI technique used in clinical applications are based on a Fourier transformation of the raw data. Alternative non-Fourier magnetic resonance imaging techniques can offer some advantages under certain conditions. SPatio-temporal ENcoding (SPEN) is a non-Fourier method that usually employs frequency-swept radio frequency pulses and can give good images in inhomogeneous magnetic fields. In this work we show how one can improve this technique by using quadratic gradients.