Magnetic moments of short-lived nuclei with part-per-million accuracy: Towards novel applications of β\beta-detected NMR in physics, chemistry and biology

We determine for the first time the magnetic dipole moment of a short-lived nucleus with part-per-million (ppm) accuracy. To achieve this two orders of magnitude improvement over previous studies, we implement a number of innovations into our $\beta$-detected Nuclear Magnetic Resonance ($\beta$-NMR) setup at ISOLDE/CERN. Using liquid samples as hosts we obtain narrow, sub-kHz linewidth, resonances, while a simultaneous in-situ $^1$H NMR measurement allows us to calibrate and stabilize the magnetic field to ppm precision, thus eliminating the need for additional $\beta$-NMR reference measurements. Furthermore, we use ab initio calculations of NMR shielding constants to improve the accuracy of the reference magnetic moment, thus removing a large systematic error. We demonstrate the potential of this combined approach with the 1.1 s half-life radioactive nucleus $^{26}$Na, which is relevant for biochemical studies. Our technique can be readily extended to other isotopic chains, providing accurate magnetic moments for many short-lived nuclei. Furthermore, we discuss how our approach can open the path towards a wide range of applications of the ultra-sensitive $\beta$-NMR in physics, chemistry, and biology.Comment: re-submitte

Hydrogen bond networks determine emergent mechanical and thermodynamic properties across a protein family

<p>Abstract</p> <p>Background</p> <p>Gram-negative bacteria use periplasmic-binding proteins (bPBP) to transport nutrients through the periplasm. Despite immense diversity within the recognized substrates, all members of the family share a common fold that includes two domains that are separated by a conserved hinge. The hinge allows the protein to cycle between open (apo) and closed (ligated) conformations. Conformational changes within the proteins depend on a complex interplay of mechanical and thermodynamic response, which is manifested as an increase in thermal stability and decrease of flexibility upon ligand binding.</p> <p>Results</p> <p>We use a distance constraint model (DCM) to quantify the give and take between thermodynamic stability and mechanical flexibility across the bPBP family. Quantitative stability/flexibility relationships (QSFR) are readily evaluated because the DCM links mechanical and thermodynamic properties. We have previously demonstrated that QSFR is moderately conserved across a mesophilic/thermophilic RNase H pair, whereas the observed variance indicated that different enthalpy-entropy mechanisms allow similar mechanical response at their respective melting temperatures. Our predictions of heat capacity and free energy show marked diversity across the bPBP family. While backbone flexibility metrics are mostly conserved, cooperativity correlation (long-range couplings) also demonstrate considerable amount of variation. Upon ligand removal, heat capacity, melting point, and mechanical rigidity are, as expected, lowered. Nevertheless, significant differences are found in molecular cooperativity correlations that can be explained by the detailed nature of the hydrogen bond network.</p> <p>Conclusion</p> <p>Non-trivial mechanical and thermodynamic variation across the family is explained by differences within the underlying H-bond networks. The mechanism is simple; variation within the H-bond networks result in altered mechanical linkage properties that directly affect intrinsic flexibility. Moreover, varying numbers of H-bonds and their strengths control the likelihood for energetic fluctuations as H-bonds break and reform, thus directly affecting thermodynamic properties. Consequently, these results demonstrate how unexpected large differences, especially within cooperativity correlation, emerge from subtle differences within the underlying H-bond network. This inference is consistent with well-known results that show allosteric response within a family generally varies significantly. Identifying the hydrogen bond network as a critical determining factor for these large variances may lead to new methods that can predict such effects.</p