HDX-MS guided drug discovery: small molecules and biopharmaceuticals

Curr Opin Struct Biol. 2014 Oct;28:105-11. doi: 10.1016/j.sbi.2014.08.007. Epub 2014 Aug 30.


Hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS or DXMS) has emerged as an important tool for the development of small molecule therapeutics and biopharmaceuticals. Central to these advances have been improvements to automated HDX-MS platforms and software that allow for the rapid acquisition and processing of experimental data. Correlating the HDX-MS profile of large numbers of ligands with their functional outputs has enabled the development of structure activity relationships (SAR) and delineation of ligand classes based on functional selectivity. HDX-MS has also been applied to address many of the unique challenges posed by the continued emergence of biopharmaceuticals. Here we review the latest applications of HDX-MS to drug discovery, recent advances in technology and software, and provide perspective on future outlook.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Deuterium / chemistry*
  • Drug Discovery / methods*
  • Drug Discovery / trends
  • Hydrogen / chemistry*
  • Mass Spectrometry / methods*
  • Mass Spectrometry / trends
  • Pharmaceutical Preparations / chemistry


  • Pharmaceutical Preparations
  • Hydrogen
  • Deuterium