Recent results in time resolved serial femtosecond crystallography at XFELs

[Display omitted] •Time-resolved serial femtosecond crystallography (tr-SFX) probes structure and function in each sample.•X-ray free electron lasers (XFELS) provide atomic and electronic structures with femtosecond temporal resolution.•Correlated multidisciplinary datasets provide deep mechanistic insights.•Synergy between X-ray free electron lasers (XFELs) and synchrotrons enable routine time-resolved studies. Time-resolved serial femtosecond crystallography (tr-SFX) methods exploit slurries of crystalline samples that range in size from hundreds of nanometers to a few tens of micrometers, at near-physiological temperature and pressure, to generate atomic resolution models and probe authentic function with the same experiment. ‘Dynamic structural biology’ is often used to encompass the research philosophy and techniques. Reaction cycles for tr-SFX studies are initiated by photons or ligand addition/mixing strategies, wherein the latter are potentially generalizable across enzymology. Thus, dynamic structural biology often creates stop-motion molecular movies of macromolecular function. In metal-dependent systems, complementary spectroscopic information can also be collected from the same samples and X-ray pulses, which provides even more detailed mechanistic insights. These types of experimental data also complement quantum mechanical and classical dynamics numerical calculations. Correlated structural-functional results will yield more detailed mechanistic insights and will likely translate into better drugs and treatments impacting human health, and better catalysis for clean energy and agriculture.