Understanding protein-drug interactions using ion mobility-mass spectrometry

Curr Opin Chem Biol. 2018 Feb:42:167-176. doi: 10.1016/j.cbpa.2017.12.013. Epub 2018 Jan 11.

Abstract

Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecules, including clinically-relevant drugs, play in these processes. We also present examples of how IM-MS can be used as a relatively rapid screening strategy to evaluate the mechanisms and conformation-driven aspects of protein:ligand interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Ion Mobility Spectrometry / methods*
  • Ligands
  • Mass Spectrometry / methods*
  • Molecular Structure
  • Pharmaceutical Preparations / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Kinases / metabolism*
  • Proteins / chemistry*
  • Proteins / metabolism*

Substances

  • Intrinsically Disordered Proteins
  • Ligands
  • Pharmaceutical Preparations
  • Proteins
  • Protein Kinases