Biological Small Angle Scattering: Techniques, Strategies and Tips

Alexander V. Grishaev

Biomolecular applications of solution X-ray and neutron scattering (SAXS and SANS, respectively) started in late 1960s - early 1970s but were relatively limited in their ability to provide a detailed structural picture and lagged behind what became the two primary methods of experimental structural biology - X-ray crystallography and NMR. However, improvements in both data analysis and instrumentation led to an explosive growth in the number of studies that used small-angle scattering (SAS) for investigation of macromolecular structure, often in combination with other biophysical techniques. Such hybrid applications are nowadays quickly becoming a norm whenever scattering data are used for two reasons. First, it is generally accepted that SAS data on their own cannot lead to a uniquely defined high-resolution structural model, creating a need for supplementing them with information from complementary techniques. Second, solution scattering data are frequently applied in situations when a method such NMR or X-ray crystallography cannot provide a satisfactory structural picture, which makes these additional restraints highly desirable. Maturation of the hybrid bio-SAS approaches brings to light new questions including completeness of the conformational space sampling, model validation, and data compatibility.