Structure determination using solution NMR: Is it worth the effort?

It has been almost 40 years since solution NMR joined X-ray crystallography as a technique for determining high-resolution structures of proteins. Since then NMR derived structure has contributed in fundamental ways to our understanding of the function of biomolecules. With the already existing mature field of X-ray crystallography and the emergence of cryo-EM as techniques to tackle high-resolution structures of large protein complexes, the role of NMR in structure determination has been questioned. However, NMR has the unique ability to recapitulate the dynamic motion of proteins in their structures, while size limitations of the biomolecular systems that can be routinely studied still present challenges. The field has continually developed methodology and instrumentation since its introduction, pushing its frontiers and redefining its limits. Here we present a brief overview of NMR-based structure determination over the past 40 years. We outline the current state of the field and look ahead to the challenges that still need to be addressed to realize the future potential of NMR as a structural technique.