Abstract
X-ray free-electron lasers (XFELs) have a unique capability for time-resolved studies of protein dynamics and conformational changes on femto- and pico-second time scales. The extreme intensity of X-ray pulses can potentially cause significant modifications to the sample structure during exposure. Successful time-resolved XFEL crystallography depends on the unambiguous interpretation of the protein dynamics of interest from the effects of radiation damage. Proteins containing relatively heavy elements, such as sulfur or metals, have a higher risk for radiation damage. In metaloenzymes, for example, the dynamics of interest usually occur at the metal centers, which are also hotspots for damage due to the higher atomic number of the elements they contain. An ongoing challenge with such local damage is to understand the residual bonding in these locally ionized systems and bond-breaking dynamics. Here, we present a perspective on radiation damage in XFEL experiments with a particular focus on the impacts for time-resolved protein crystallography. We discuss recent experimental and modelling results of bond-breaking and ion motion at disulfide bonding sites in protein crystals.
Highlights
Time-resolved protein crystallography has developed into a powerful capability of X-ray free-electron laser sources (XFELs) [1,2]
A closer examination of the physics of XFEL radiation damage suggests that radiation damage is an ongoing concern for the success of time-resolved XFEL crystallography experiments
We have reviewed XFEL damage processes with a particular focus on recent theoretical and experimental developments concerning local damage “hot spots” and molecular damage effects
Summary
Time-resolved protein crystallography has developed into a powerful capability of X-ray free-electron laser sources (XFELs) [1,2]. Local damage is not independent of the spatial arrangement of the atoms It occurs when there is significant variation in the ionization rates of different elements or when certain ions exhibit reproducible, non-thermal motion [13]. Previous reviews of XFEL damage have given significant attention to the progress in understanding global damage and how SFX has achieved its successes to date [5,10] It is the subtler effects of local damage, which are not so well understood, which may have greater relevance to future time-resolved experiments, especially those that push the boundaries of high beam intensity and high time resolution. We present new quantum simulations of a disulfide bond breaking to illustrate these future directions
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