Macromolecular X-ray crystallography (MX) is the most powerful method for structure determination of biological molecules. Last year 91% of all new Protein Data Bank deposits (10,121) were solved using X-rays, and over 90% of these were determined using synchrotron radiation. MX is essential for basic, biomedical and environmental research, drug discovery and biotechnology. In the US, the APS is the largest and the most productive light source for MX. The APS upgrade (APS-U) to a multi-bend achromat (MBA) lattice will deliver the ultimate X-ray source that will radically transform MX capabilities. The brilliant, micron-size, stable X-ray beams will become routinely available to a large number of users at more than a dozen MX stations 24 hrs/day, 200 days/year. Advanced MX methods at APS-U beamlines utilizing microcrystals will allow static, dynamic and time resolved macromolecular studies at unmatched speed and scale, wide range of temperatures (10 – 350 K), providing high-resolution and atomic insight. The APS-U integrated suites of experimental and computational capabilities will examine biological molecules at subnanometer to millimeter length, on time scales from picoseconds to seconds and at different temperatures and pressures. This will make APS-U a powerful one-of-a-kind tool for structural biology.

The specific advantages of APS-U X-ray source are (i) highly parallel X-ray beams that will be essential to study large macromolecular complexes at high resolution, (ii) increased brightness that will allow beamlines to deliver intense micrometer sized beams, resulting in a 100-fold improvement in signal-to-noise, (iii) increased brightness at high energy that can be exploited to  reduce primary radiation damage due to escape of photoelectrons that cause most of the damage from the X-ray beam footprint, and (iv) high-speed detectors that will allow a reduction of secondary radiation damage at room temperature by using very short exposures to  “out-run” free-radical diffusion.  The source will also be ideal to exploit macromolecular systems in situ and in cellulo.

In a context where new technologies for structure determination emerge, such as free electron lasers and cryo-electron microscopy, this workshop will explore how these future structural biology resources can be used to address grand challenges in biology for predictive understanding of the relationship between the genome, structure, function, and interactions important for research relevant to DOE energy, biological and environmental missions, and NIH human health and well-being missions.