Structural Biology: A Century-long Journey into an Unseen World

When the first atomic structures of salt crystals were determined by the Braggs in 1912–1913, the analytical power of X-ray crystallography was immediately evident. Within a few decades the technique was being applied to the more complex molecules of chemistry and biology and is rightly regarded as the foundation stone of structural biology, a field that emerged in the 1950s when X-ray diffraction analysis revealed the atomic architecture of DNA and protein molecules. Since then the toolbox of structural biology has been augmented by other physical techniques, including nuclear magnetic resonance spectroscopy, electron microscopy, and solution scattering of X-rays and neutrons. Together these have transformed our understanding of the molecular basis of life. Here I review the major and most recent developments in structural biology that have brought us to the threshold of a landscape of astonishing molecular complexity.