Abstract
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 language | English |
|---|---|
| Journal | PLoS Computational Biology |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2014 |
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ASJC Scopus subject areas
- Computational Theory and Mathematics
- Modelling and Simulation
- Ecology, Evolution, Behavior and Systematics
- Genetics
- Molecular Biology
- Ecology
- Cellular and Molecular Neuroscience
Cite this
Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry : The Human Insulin Dimer. / Li, Jinyu; Rossetti, Giulia; Dreyer, Jens; Raugei, Simone; Ippoliti, Emiliano; Lüscher, Bernhard; Carloni, Paolo.
In: PLoS Computational Biology, Vol. 10, No. 9, 01.09.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry
T2 - The Human Insulin Dimer
AU - Li, Jinyu
AU - Rossetti, Giulia
AU - Dreyer, Jens
AU - Raugei, Simone
AU - Ippoliti, Emiliano
AU - Lüscher, Bernhard
AU - Carloni, Paolo
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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.
AB - 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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U2 - 10.1371/journal.pcbi.1003838
DO - 10.1371/journal.pcbi.1003838
M3 - Article
C2 - 25210764
AN - SCOPUS:84907587688
VL - 10
JO - PLoS Computational Biology
JF - PLoS Computational Biology
SN - 1553-734X
IS - 9
ER -