ABSTRACT
Since the early 1990s, nuclear magnetic resonance (NMR) Spectroscopy has developed into an extremely powerful tool for solving macromolecular structures. The combination of innovations in magnet and probe design, pulse programming, isotopic labeling, data analysis, and computational methods means that larger protein structures can now be solved more easily than ever before. Historically, NMR has been limited to very small proteins (initially those under ~10 kDa), but current methods allow for determination of structures as large as 30-40 kDa. This size limit is being pushed as new techniques challenge the fundamental resolution limit of NMR spectroscopy, enabling the acquisition of high-field spectra with better resolution than was previously possible (1). Solution structures of proteins in the 60kDa range are now within reach (2), and systems larger than 100 kDa have been studied (3), although a complete structure of this size has not yet been reported. Since fewer than 6% of crystal structures in the Protein Data Bank (PDB) (4) are larger than 60 kDa, NMR and X-ray crystallography are both viable techniques for most protein structure determinations.
