Neutron Macromolecular Crystallography for Biological Samples—Current State and Future Perspectives

Abstract

Knowledge of hydrogen locations and protonation states is critical for a fundamental understanding of biological macromolecular function/interactions, and neutron macromolecular crystallography (NMX) is uniquely suited among the experimental structural-determination methods to provide this information. However, despite its potential, NMX remains a relatively niche technique, due to substantial limitations. This review explores NMX’s role amongst the evolving landscape of structural biology, comparing and contrasting it to the historical gold standard of X-ray macromolecular crystallography (X-ray MX) and the increasingly prevalent electron-based methods—i.e., electron microscopy (EM) and electron diffraction (ED). Forthcoming developments (e.g., the European Spallation Source in Lund, Sweden, coming online) are expected to substantially address current limitations and ensure NMX will remain relevant in the coming decades.