Current approaches for integrating solution NMR spectroscopy and small-angle scattering to study the structure and...

The study of complex and dynamic biomolecular assemblies is a key challenge in structural biology and requires the use of multiple methodologies providing complementary spatial and temporal information. NMR spectroscopy is a powerful technique that allows high-resolution structure determination of biomolecules as well as investigating their dynamic properties in solution. However, for high-molecular-weight systems, such as biomolecular complexes or multi-domain proteins, it is often only possible to obtain sparse NMR data, posing significant challenges to structure determination. Combining NMR data with information obtained from other solution techniques is therefore an attractive approach. The combination of NMR with small-angle X-ray and/or neutron scattering has been shown to be particularly fruitful. These scattering approaches provide low-resolution information of biomolecules in solution and reflect ensemble-averaged contributions of dynamic conformations for scattering molecules up to megadalton molecular weight. Here, we review recent developments in the combination of nuclear magnetic resonance spectroscopy (NMR) and small-angle scattering (SAS) experiments. We briefly outline the different types of information that are provided by these techniques. We then discuss computational methods that have been developed to integrate NMR and SAS data, particularly considering the presence of dynamic structural ensembles and flexibility of the investigated biomolecules. Finally, recent examples of the successful combination of NMR and SAS are presented to illustrate the utility of their combination.