Macromolecular crystallography at synchrotron radiation sources: current status and future developments

Abstract

X-ray diffraction with synchrotron radiation (SR) has revealed the atomic structures of numerous biological macromolecules including proteins and protein complexes, nucleic acids and their protein complexes, viruses, membrane proteins and drug targets. The bright SR X-ray beam with its small divergence has made the study of weakly diffracting crystals of large biological molecules possible. The ability to tune the wavelength of the SR beam to the absorption edge of certain elements has allowed anomalous scattering to be exploited for phase determination. We review the developments at synchrotron sources and beamlines from the early days to the present time, and discuss the significance of the results in providing a deeper understanding of the biological function, the design of new therapeutic molecules and time-resolved studies of dynamic events using pump–probe techniques. Radiation damage, a problem with bright X-ray sources, has been partially alleviated by collecting data at low temperature (100 K) but work is ongoing. In the most recent development, free electron laser sources can offer a peak brightness of hard X-rays approximately 10 8 times brighter than that achieved at SR sources. We describe briefly how early experiments at FLASH and Linear Coherent Light Source have shown exciting possibilities for the future.