High-resolution mass spectrometry of small molecules bound to membrane proteins

Nat Methods. 2016 Apr;13(4):333-6. doi: 10.1038/nmeth.3771. Epub 2016 Feb 22.


Small molecules are known to stabilize membrane proteins and to modulate their function and oligomeric state, but such interactions are often hard to precisely define. Here we develop and apply a high-resolution, Orbitrap mass spectrometry-based method for analyzing intact membrane protein-ligand complexes. Using this platform, we resolve the complexity of multiple binding events, quantify small molecule binding and reveal selectivity for endogenous lipids that differ only in acyl chain length.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lipids / chemistry*
  • Mass Spectrometry / methods*
  • Membrane Proteins / metabolism*
  • Models, Molecular
  • Peptide Fragments / metabolism*
  • Protein Binding
  • Small Molecule Libraries / metabolism*


  • Lipids
  • Membrane Proteins
  • Peptide Fragments
  • Small Molecule Libraries