Time-resolved small-angle neutron scattering (TR-SANS) for structural biology of dynamic systems: Principles, recent developments, and practical guidelines

We present an overview of time-resolved small-angle neutron scattering (TR-SANS) applied to biological systems, with a focus on bio-macromolecules and assemblies they form, together with practical guidelines. After a brief introduction to the theory and practice of SANS, we present the general setup and specifics of time-resolved experiments, as well as an overview of diverse experimental results and applications from the past ≈25years. Subsequently, we provide guidelines and practical instructions for the design, planning and execution for TR-SANS experiments, as a function of the time- and length-scales of the biological processes of interest, the availability of sample amount and deuterium labeling, and the structural information sought. We conclude with a discussion of the most recent instrumental and sample environment developments and perspectives for the future.