Hydrogen-deuterium exchange mass spectrometry for determining protein structural changes in drug discovery

Abstract

Protein structures are dynamically changed in response to post-translational modifications, ligand or chemical binding, or protein-protein interactions. Understanding the structural changes that occur in proteins in response to potential candidate drugs is important for predicting the modes of action of drugs and their functions and regulations. Recent advances in hydrogen/deuterium exchange mass spectrometry (HDX-MS) have the potential to offer a tool for obtaining such understanding similarly to other biophysical techniques, such as X-ray crystallography and high resolution NMR. We present here, a review of basic concept and methodology of HDX-MS, how it is being applied for identifying the sites and structural changes in proteins following their interactions with other proteins and small molecules, and the potential of this tool to help in drug discovery.