Early days of protein hydrogen exchange: 1954-1972

Hydrogen exchange (HX) is recognized today as one of the most powerful and versatile tools available to protein scientists, especially for studying protein conformational change. This short history traces the beginnings of the HX method and the basic problems that faced the founders. Protein HX began as a simple idea with a straightforward goal, but the first experiments revealed both the unexpected complexity of the subject and the potential power of the method for probing deep into how proteins work. By 1972, the chemistry of the exchange reaction in peptides began to be well understood, but the challenge of getting and interpreting data on HX for individual peptide NH protons in proteins remained for decades longer.