Emerging opportunities in structural biology with X-ray free-electron lasers

X-ray free-electron lasers (X-FELs) produce X-ray pulses with extremely brilliant peak intensity and ultrashort pulse duration. It has been proposed that radiation damage can be 'outrun' by using an ultra intense and short X-FEL pulse that passes a biological sample before the onset of significant radiation damage. he concept of 'diffraction-before-destruction' has been demonstrated recently at the Linac Coherent Light Source, the first operational hard X-ray FEL, for protein nanocrystals and giant virus particles. The continuous diffraction patterns from single particles allow solving the classical 'phase problem' by the oversampling method with iterative a gorithms. If enough data are collected from many identical copies of a (biological) particle, its three-dimensional structure can be reconstructed. We review the current status and future prospects of serial femtosecond crystallography (SFX) and single-particle coherent diffraction imaging (CDI) with X-FELs.