950 MHz NMR spectrometer with cryo probe

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Integrative structural biology combining X-ray crystallography, cryo-electron microscopy and NMR spectroscopy nowadays provides molecular details for essential biological processes that underlie physiological and disease-linked cellular pathways. Understanding these complex molecular mechanisms is not possible with static structures but critically requires an understanding of functionally important conformational dynamics of proteins, RNAs and their complexes. NMR spectroscopy is the only method that can describe the dynamic properties of biological macromolecules at (near-) atomic resolution for timescales ranging from picoseconds to hours. To study molecular mechanisms of proteins, RNAs and their complexes in a native-like solution environment, NMR spectroscopy at ultra-high magnetic fields is essential to improve signal-to-noise and spectral resolution. Moreover, about a third of the human proteome comprises intrinsically disordered regions and proteins (IDRs/IDPs), which often play essential roles to regulate cellular processes, play important roles in the formation a regulation of membrane-less organelles by liquid-liquid phase separation and are linked to human disease, ranging from cancer to neurodegenerative disorders. These regions can only be addressed by solution NMR techniques, but require increased spectral resolution due to the degeneracy of their amino acid composition. Continuous developments in NMR hardware, NMR methodology and sample preparation and isotope labeling methods have opened up new possibilities to study biomedically relevant biomolecular systems with solution state NMR. In this proposal, we apply for the permanent installation of the 950 MHz ultra-high-field NMR spectrometer at the Bayerische NMR-Zentrum. This is in connection with an accompanying proposal for a 0.7 mm MAS solid-state NMR probe for the recently installed 1.2 GHz spectrometer. Following recommendations of the international Scientific Advisory Board (SAB) of the BNMRZ, we plan to reserve 50% of the measurement time at the 1.2 GHz instrument for ultrafast MAS solid-state NMR applications to take advantage of the outstanding improvements in sensitivity and resolution. The resulting reduction in measurement time available for solution- state applications at 1.2 GHz will be compensated by the 950 MHz instrument, which will be used exclusively for solution state experiments supporting the increasing number of projects that require ultra-high-field solution NMR measurements.