Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry: The Human Insulin Dimer

Jinyu Li, Giulia Rossetti, Jens Dreyer, Simone Raugei, Emiliano Ippoliti, Bernhard Lüscher, Paolo Carloni

Research output: Contribution to journalArticle

9 Citations (Scopus)


Protein electrospray ionization (ESI) mass spectrometry (MS)-based techniques are widely used to provide insight into structural proteomics under the assumption that non-covalent protein complexes being transferred into the gas phase preserve basically the same intermolecular interactions as in solution. Here we investigate the applicability of this assumption by extending our previous structural prediction protocol for single proteins in ESI-MS to protein complexes. We apply our protocol to the human insulin dimer (hIns2) as a test case. Our calculations reproduce the main charge and the collision cross section (CCS) measured in ESI-MS experiments. Molecular dynamics simulations for 0.075 ms show that the complex maximizes intermolecular non-bonded interactions relative to the structure in water, without affecting the cross section. The overall gas-phase structure of hIns2 does exhibit differences with the one in aqueous solution, not inferable from a comparison with calculated CCS. Hence, care should be exerted when interpreting ESI-MS proteomics data based solely on NMR and/or X-ray structural information.

Original languageEnglish
JournalPLoS Computational Biology
Issue number9
Publication statusPublished - Sep 1 2014


ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modelling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

Cite this