Methodological trends in structural biology

摘要

Structural biology has witnessed tremendous developments from the dawn of the new millennium. Macromolecular crystallography, which since its foundation around the ‘50s of the twenties century has been the stronghold of the technique, has finally reached its full maturity, thanks to several major technical improvements: the building of third (and now forth) generation synchrotron sources and the use of very fast high-resolution detectors allow to collect an entire diffraction data set in a matter of seconds; thanks to the dramatic improvements of computing power, these data can be processed very quickly and often (despite not in all cases) the structure can be solved and refined in days or weeks; the phase problem, the major stumbling block towards a fully automatized solution of the structure, is still present, but it has been overcome in the vast majority of cases thanks to the use of various techniques, from molecular replacement to anomalous scattering 1–5. The only aspect in which developments have not kept pace is the crystallization process that, despite some significant improvements, still represents the greatest obstacle on the way towards a fast and fully automatized determination of the 3D structure of a macromolecule. Growing crystals can be in most cases a very long and painful process that often requires a significant amount of starting pure material 6.