Unfolding the history of protein HDX NMR

I review the development of two-dimensional hydrogen-deuterium exchange (HDX) nuclear magnetic resonance (NMR) spectroscopy and highlight its importance to the study of protein structure and stability. This review presents a historical perspective beginning from the discovery of deuterium and its early uses, to the era of Linderstrøm-Lang and mechanistic studies, to the development of NMR and how the techniques came together to provide residue-level insight. I discuss recent developments, new applications, and offer a perspective about the future.