Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications

Drug Discov Today. 2014 Jan;19(1):95-102. doi: 10.1016/j.drudis.2013.07.019. Epub 2013 Aug 6.


The higher order structure of protein therapeutics can be interrogated with hydrogen/deuterium exchange mass spectrometry (HDX-MS). HDX-MS is now a widely used tool in the structural characterization of protein therapeutics. In this review, HDX-MS based workflows designed for protein therapeutic discovery and development processes are presented, focusing on the specific applications of epitope mapping for protein/drug interactions and biopharmaceutical comparability studies. Future trends in the application of HDX-MS in protein therapeutics characterization are also described.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Deuterium / chemistry*
  • Humans
  • Hydrogen / chemistry*
  • Mass Spectrometry / methods*
  • Protein Binding / physiology
  • Protein Interaction Maps / physiology*
  • Protein Structure, Secondary
  • Protein Transport / physiology


  • Hydrogen
  • Deuterium