Abstract
Radiation damage is still the most limiting factor in obtaining high-resolution structures of macromolecules in crystallographic experiments at synchrotrons. With the advent of X-ray free-electron lasers (XFELs) that produce ultrashort and highly intense X-ray pulses, it became possible to outrun most of the radiation-damage processes occurring in the sample during exposure to XFEL radiation. Although this is generally the case, several experimental and theoretical studies have indicated that structures from XFELs may not always be radiation-damage free. This is especially true when higher intensity pulses are used and protein molecules that contain heavy elements in their structures are studied. Here, the radiation-damage mechanisms that occur in samples exposed to XFEL pulses are summarized, results that show indications of radiation damage are reviewed and methods that can partially overcome it are discussed.
Highlights
Macromolecular X-ray crystallography (MX) has been the most powerful approach for obtaining three-dimensional structural information on biological species such as proteins, nucleic acids or viruses at up to atomic resolution which, together with functional studies, is crucial for understanding the mechanism underlying the given biological process (Shi, 2014)
The peak brightness of X-ray free-electron lasers (XFELs) sources exceeds those of conventional laboratory and synchrotron X-ray sources that are suitable for MX applications by orders of magnitude (Patterson, 2014)
This work reviews the current knowledge on the mechanisms of ultrafast radiation damage to atoms in samples exposed to high-intensity XFEL radiation, compares the effects of radiation damage caused by XFEL pulses in protein crystals with the well known types of damage observed in MX at synchrotron sources, highlights studies that have observed indications of radiation damage in SFX data and discusses methods to minimize radiation damage at XFELs
Summary
Macromolecular X-ray crystallography (MX) has been the most powerful approach for obtaining three-dimensional structural information on biological species such as proteins, nucleic acids or viruses at up to atomic resolution which, together with functional studies, is crucial for understanding the mechanism underlying the given biological process (Shi, 2014). The peak brightness of XFEL sources exceeds those of conventional laboratory and synchrotron X-ray sources that are suitable for MX applications by orders of magnitude (Patterson, 2014) It has been predicted (Neutze et al, 2000) and verified experimentally (Chapman et al, 2011) that diffraction data can be obtained using these highly intense and femtosecond duration pulses before signs of radiation damage are observed, at high resolution (Boutet et al, 2012) and even when the dose absorbed by the crystal is orders of magnitude higher than the radiationdose limits established as being safe at conventional X-ray sources (Garman & Weik, 2017). This work reviews the current knowledge on the mechanisms of ultrafast radiation damage to atoms in samples exposed to high-intensity XFEL radiation, compares the effects of radiation damage caused by XFEL pulses in protein crystals with the well known types of damage observed in MX at synchrotron sources, highlights studies that have observed indications of radiation damage in SFX data and discusses methods to minimize radiation damage at XFELs
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