Destruction during diffraction: radiation damage in macromolecular structure determination

Abstract
Structural biology relies on X-ray crystallography to provide much of the three-dimensional information on proteins and other macromolecules that informs biological function. However, radiation damage (RD) to the samples remains one of the major bottlenecks to accurate structure determination. The RD can manifest as `global’ changes manifesting as the fading of the diffraction pattern with increasing dose, or as `specific’ structural and chemical alterations in the resulting protein structures. While mostly observed in data collected at synchrotron X-ray sources, XFEL data (‘diffraction before destruction’) are not immune from RD effects. Detection and avoidance of RD artefacts have traditionally proved challenging, but strategies will be summarised in this talk.