A Personal Perspective on Metalloprotein Structure and the Future of Macromolecular X‐Ray Crystallography

ABSTRACT This perspective considers the role of X‐ray crystallography for the study of metalloproteins in the era of cryogenic electron microscopy and machine learning models. While X‐ray crystallography may in the future play a smaller role in the routine structural analysis of all but the smallest metalloproteins, it is well suited for “multi‐messenger” studies combining structure and spectroscopy on the same sample, time resolved studies, and deriving charge densities, the electrostatic potential and other properties from accurate diffraction data. Sunney Chan's approach of keeping his research fresh by working on complex and important problems, while remaining connected to the fundamentals, provides excellent guidance for moving forward in this new era of structural biology.