Protein structure determination using sparse NMR data.

Advances in hardware, sample preparation, pulse sequence development and refinement techniques have enabled NMR to study systems in solution that previously were in the exclusive realm of X-ray crystallography with immense benefits for structural biology. NMR studies might succeed where crystallisation or phasing of diffraction data fails and can be used to check crystal structures for artefacts due to crystal packing, crystallisation additives or cryotemperatures. Moreover, NMR has the unique ability to probe dynamics and to probe dynamics and to characterise lowly populated conformational states during binding processes,1-3 conformational transitions,4-7 and protein folding. Dispite this progress, MR de nova structure determination on systems that exceed 20 kDa in molecular weight remains dhallenging due to increased linewidth and spectral crowding.9-12  The linewidths increase with slower molecular tumbling, and hence even pose a problem when only part of the biomolecule is NMR wisible, while other parts (binding partners, additional domains or detergent micelles) are made NBR-invisible by deuteration. ..