Personal remarks on the future of protein crystallography and structural biology.

Abstract

Protein crystallography, the main experimental method of structural biology, has undergone in the recent past three revolutionary changes leading to its unexpected renaissance. They were connected with (i) the introduction of synchrotron radiation sources for X-ray diffraction experiments, (ii) implementation of Se-Met multiwavelength anomalous diffraction (MAD) for phasing, and (iii) initiation of structural genomics (SG) programs. It can be foreseen that in the next 10-15 years protein crystallography will continue to be in this revolutionary phase. We can expect not only an avalanche of protein crystal structures from SG centers, but also attacking of more demanding projects, such as the structure of membrane proteins and of very large macromolecular complexes. On the technological front, the introduction of X-ray radiation from free-electron lasers will revolutionize the experimental possibilities, making feasible even the imaging of single molecules and of intact biological cells.

Resolution of protein structure by mass spectrometry

“…The very latest advances in protein crystallography allow one to map macromolecular dynamics, which is still in its infancy. ‘Structure photographs’ are taken by recording a complete diffraction pattern in about 1 ns (Jaskolski, ). Eventually, X‐ray beams many billions of times brighter will allow the diffraction pattern of a single molecule to be collected, which will bypass the need for a crystal altogether (Hajdu, ).…”