Computational mass spectrometry

Native electrospray ionization/ion mobility-mass spectrometry (ESI/IM-MS) is emerging as a powerful technique for capturing key structural features of proteins and their complexes. Next to the mass-to-charge ratio (m/z), it provides the charge state distributions (CSD) and collision cross sections (CCS) for all species present in the gas phase. From these, one can extract their stoichiometry, solvent-accessible surface area (SASA), dynamics and shape, as well as distribution of copopulated assembly and folding states.  In spite of lacking atomic resolution, ESI/IM-MS has distinct advantages over high-resolution methods such as X-ray crystallography NMR spectroscopy, as well as, lower resolution techniques such as cryo-electron microscopy and tomography. Indeed, it does not require crystallization and it is already sensitive at biomolecule concentrations well (roughly 1000 times) below those required for most of these techniques.  In addition, it can characterize species distributions, i.e., copopulated folding and assembly states of proteins and complexes. The structural information derived from ESI/IM-MS measurements can guide computational modeling by experimental constraints to achieve high-resolution structural description of proteins and protein complexes in solution and in the gas phase.

To further advance the impact of ESI/IM-MS for structural biology, it is imperative to quantify the impact of the absence of solvent (as experienced by the protein ions mass in spectrometry experiments) on protein structure and dynamics. Molecular simulations, performed by several groups including ours, provide atomistic models of proteins under ESI/IM-MS conditions, consistent with available, low-resolution ESI/IM-MS structural data and charge states.

People involved

  • Institute for Advanced Simulation (IAS)
  • Computational Biomedicine (IAS-5 / INM-9)
Building 16.15 /
Room 3010
+49 2461/61-8941

Prof. Rita Grandori

Associate professor

    +39 0264483363
    +39 0264483395


    +34 93 40 37156


    1. Conformational effects in protein electrospray-ionization mass spectrometry. Li J, Santambrogio C, Brocca S, Rossetti G, Carloni P, Grandori R. Mass Spectrom Rev. 2016. 35(1): 111-22.
    2. Proton Dynamics in Protein Mass Spectrometry. Li J, Lyu W, Rossetti G, Konijnenberg A, Natalello A, Ippoliti E, Orozco M, Sobott F, Grandori R, Carloni P. J Phys Chem Lett. 2017. 8(6): 1105-1112.
    3. Structure and dynamics of oligonucleotides in the gas phase. Arcella A, Dreyer J, Ippoliti E, Ivani I, Portella G, Gabelica V, Carloni P, Orozco M. Angew Chem Int Ed Engl. 2015. 54(2): 467-71.
    4. Role of hydrophobic residues for the gaseous formation of helical motifs. Liu L, Dong X, Liu Y, Österlund N, Gräslund A, Carloni P, Li J. Chem Commun (Camb). 2019. 55(35): 5147-5150.
    5. A computational model for protein ionization by electrospray based on gas-phase basicity. Marchese R, Grandori R, Carloni P, Raugei S. J Am Soc Mass Spectrom. 2012. 23(11): 1903-10.
    6. Molecular simulation-based structural prediction of protein complexes in mass spectrometry: the human insulin dimer. Li J, Rossetti G, Dreyer J, Raugei S, Ippoliti E, Lüscher B, Carloni P. PLoS Comput Biol. 2014. 10(9): e1003838.
    7. On the zwitterionic nature of gas-phase peptides and protein ions. Marchese R, Grandori R, Carloni P, Raugei S. PLoS Comput Biol. 2010. 6(5): e1000775.
    8. Molecular basis for structural heterogeneity of an intrinsically disordered protein bound to a partner by combined ESI-IM-MS and modeling. D'Urzo A, Konijnenberg A, Rossetti G, Habchi J, Li J, Carloni P, Sobott F, Longhi S, Grandori R. J Am Soc Mass Spectrom. 2015. 26(3): 472-81.
    Last Modified: 11.06.2022