Hydrogen exchange and mass spectrometry: A historical perspective

Protein molecules naturally emit streams of information-rich signals in the language of hydrogen exchange concerning the intimate details of their stability, dynamics, function, changes therein, and effects thereon, all resolved to the level of their individual amino acids. The effort to measure protein hydrogen exchange behavior, understand the underlying chemistry and structural physics of hydrogen exchange processes, and use this information to learn about protein properties and function has continued for 50 years. Recent work uses mass spectrometric analysis together with an earlier proteolytic fragmentation method to extend the hydrogen exchange capability to large biologically interesting proteins. This article briefly reviews the advances that have led us to this point and the understanding that has so far been achieved.