Preprints  

This manuscript describes a method for determining the solution structure of a solvent-exposed polypeptide segment (the L3 loop), which is next to the active site of the penicillin-degrading enzyme IMP-1. Tagging three different sites on the protein with paramagnetic metal ions allowed positioning the L3 loop with atomic resolution.

This work provides some clarifications on the long known Redfield theory of spin relaxation, which considers a small system coupled to a large ensemble of particles in thermodynamic equilibrium. The derivation is rewritten so as to emphasize the usual assumptions and their consequences. In particular, the respective roles of the detailed balance balance assumption, as well as the non commutativity of the spin-bath coupling are discussed.

We describe a suite of experiments that exploit field-dependent relaxation measurements of four spin transitions in methyl groups to characterise chemical exchange processes, and which can be used as an alternative or complement to CPMG relaxation dispersion measurements. We show that these four spin transitions benefit from the methyl TROSY effect, and so provide a unique combination of slow intrinsic relaxation and high sensitivity to chemical exchange.

We present the on-going work of a large, community initiative to establish standards for the processing of nonuniformly sampled NMR experiments. The NUScon software, contest, and archive of spectral evaluation data provide a comprehensive platform for addressing the most challenging questions related to NUS experiments. We will run annual contests and generate a database of results, which will empower us to guide the NUS community towards a set of best practices.

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.

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 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.