Traveling‐wave ion mobility mass spectrometry of protein complexes: accurate calibrated collision cross‐sections of human insulin oligomers

Salbo, Rune; Bush, Matthew F.; Naver, Helle; Campuzano, Iain D. G.; Robinson, Carol V.; Pettersson, Ingrid; Jørgensen, Thomas J. D.; Haselmann, Kim F.

doi:10.1002/rcm.6211

Cited by 148 publications

(195 citation statements)

References 67 publications

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“…This is q = 6+ [52]. We used the fact that the charge state of protein ions with the apparent gas-phase basicity (GB app , see its definition in the Text S1) close to the GB of the solvent, from which the protein ions are formed, reproduces the experimental maximum charge states under ESI.…”

Section: Resultsmentioning

confidence: 99%

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

Rossetti

Dreyer

et al. 2014

PLoS Comput Biol

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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.

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Section: Resultsmentioning

confidence: 99%

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

Rossetti

Dreyer

et al. 2014

PLoS Comput Biol

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“…Peak assignment is also more secure if exactly the same instrument source and ion transfer geometries are used for the calibration and the experiment. For this reason, a modified Waters Synapt in which the SRIG is operated in a drift tube mode (without travelling waves) [38,[45][46][47] was built and calibration data were recorded. In the future, an inter-laboratory calibration would be useful to identify the most reliable and robust calibrants.…”

Section: Journal Ofmentioning

confidence: 99%

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

D’Atri¹,

Porrini²,

Rosu³

et al. 2015

J. Mass Spectrom.

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Ion mobility spectrometry experiments allow the mass spectrometrist to determine an ion's rotationally averaged collision cross section Ω EXP . Molecular modelling is used to visualize what ion three-dimensional structure(s) is(are) compatible with the experiment. The collision cross sections of candidate molecular models have to be calculated, and the resulting Ω CALC are compared with the experimental data. Researchers who want to apply this strategy to a new type of molecule face many questions: (1) What experimental error is associated with Ω EXP determination, and how to estimate it (in particular when using a calibration for traveling wave ion guides)? (2) How to generate plausible 3D models in the gas phase? (3) Different collision cross section calculation models exist, which have been developed for other analytes than mine. Which one(s) can I apply to my systems? To apply ion mobility spectrometry to nucleic acid structural characterization, we explored each of these questions using a rigid structure which we know is preserved in the gas phase: the tetramolecular G-quadruplex [dTGGGGT] 4 , and we will present these detailed investigation in this tutorial. Additional supporting information may be found in the online version of this article at the publisher's web site.Keywords: ion mobility spectrometry; collision cross section; structure; nucleic acids; simulations; molecular modeling; gas-phase ion structure IntroductionElectrospray mass spectrometry (ESI-MS) in native conditions can preserve the structures of biomolecules and separate them according to their mass-to-charge ratios. [1,2] Ion mobility spectrometry (IMS) separates ions according to their size-to-charge ratios in the gas-phase. [3][4][5][6] Size is related to the mass (or number of atoms) and to the three-dimensional shape of a molecule. Therefore, by hyphenating IMS to mass spectrometry (IM-MS), one can sort ions according to both mass and shape. The challenge is to decipher structural information from ion mobility experiments. [7][8][9] The physical quantity characterizing the shape is the collision cross section (CCS), [10] which will be introduced in more detail in the Section on Ion mobility and collision cross sections. The present tutorial clarifies how to interpret CCS measurements in terms of three-dimensional structure for ions larger than 100 atoms extracted from the solution by electrospray ionization (ESI). The gold standard is to match CCSs experimentally obtained from IMS with CCSs calculated for modelling three-dimensional structures of the ion of interest. We will discuss the factors that can affect the precision (reproducibility) and accuracy in both the measurements and the calculations. Understanding each of these factors is crucial to interpret quantitative matches confidently and assess the meaningfulness of structural assignments.On the experimental side, we will describe the determination of CCS from traveling wave ion mobility spectrometers and from drift tube ion mobility spectrometers, with example data recorde...

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“…[3][4][5][6][7][8][9][10][11] The principles of TWIMS have been described in more detail elsewhere. 2 However, in summary, the drift cell contains paired electrodes that create a pulsed voltage which carries the ions through the drift cell as a travelling wave.…”

Section: Eqn2mentioning

confidence: 99%

“…There are several reports on the application of this method to the study of metabolites, 4,5 proteins and peptides. [6][7][8][9][10] Arenes and adamantanes have been studied by TWIMS and their experimental and theoretical CCS investigated. 11 Napthalene, phenanthrene and pyrene were analysed in helium and nitrogen drift gases to determine CCS, which were then compared to modelled data.…”

Section: Eqn2mentioning

confidence: 99%

Structural studies of metal ligand complexes by ion mobility-mass spectrometry

Wright

Castro-Gómez

Jurneczko

et al. 2013

Int. J. Ion Mobil. Spec.

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Traveling‐wave ion mobility mass spectrometry of protein complexes: accurate calibrated collision cross‐sections of human insulin oligomers

Cited by 148 publications

References 67 publications

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

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

Linking molecular models with ion mobility experiments. Illustration with a rigid nucleic acid structure

Structural studies of metal ligand complexes by ion mobility-mass spectrometry

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