Potential impact of an X-ray free electron laser on structural biology

Recent developments in X-ray source technology provide new opportunities for both the rapid imaging of macromolecules in three dimensions, and the observation of short-lived structural intermediates in light-sensitive macromolecules. Pioneering time-resolved X-ray diffraction studies on macromolecules have laid the foundations for similar studies on increasingly complex macromolecular systems at developing X-ray sources. In addition, the increased peak brilliance expected from an X-ray free electron laser source opens the possibility of new imaging technologies for determining X-ray structures from systems which do not readily yield well-diffracting crystals. Here we review the potential impact of extreme brilliance free electron laser X-ray sources on structural biology. We both sketch the biological case for sub-picosecond X-ray studies of light-sensitive proteins and describe the new imaging possibilities which will emerge through ultrafast X-ray imaging. A central issue is that of X-ray-induced radiation damage on macromolecular samples, and the advantages in this context of working in the femtosecond regime, are discussed. r 2004 Elsevier Ltd. All rights reserved.