Macromolecular crystallography

Abstract

Crystallography provides structural evidence of macromolecules in atomic detail. However, the atomic structure is not the direct outcome of the experiment. Diffraction data need to be processed and the phase problem must be solved to visualize the map from which an atomic model of the macromolecule is interpreted and iteratively improved. Despite this complex process from sample to scientific answer, crystallography is widely accessible in biochemical and biological research. Easy access to the experimental set-ups, free software for academic use and complimentary analytical computing, supported by automation and expert assistance, makes crystallography available to non-crystallographers. This Primer offers a practical and rational introduction to macromolecular crystallography, whether to engage directly or to critically assess results, with a focus on understanding the diffraction data, solving the phase problem, building and refining the atomic model, and interpreting the resulting atomic structure. We provide an overview of what crystallography can achieve, the key decisions and trade-offs involved, and how to evaluate outcomes effectively.