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Probabilistic model applied to ion abundances in product-ion spectra: quantitative analysis of aspartic acid isomerization in peptides

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Abstract

Evaluation of post-translational modifications of protein molecules is important for both basic and applied biomedical research. Mass spectrometric quantitative studies of modifications, which do not change the mass of the protein, such as isomerization of aspartic acid, do not necessarily require the use of isotope-labelled standards. However, the accurate solution of this problem requires a deep understanding of the relationship between the mole fractions of the isomers and the peak intensities in the mass spectra. In previous studies on the isomerization of aspartic acid in short beta-amyloid fragments, it has been shown that calibration curves used for such quantitative studies often have a non-linear form. The reason for the deviation in the shape of the calibration curves from linearity has not yet been established. Here, we propose an explanation for this phenomenon based on a probabilistic model of the fragmentation process and present a general approach for the selection of fragments that can be used for quantitative studies of the degree of isomerization.

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Funding

The research was supported by the Russian Scientific Foundation Grant No. 16-14-00181.

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Authors and Affiliations

  1. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygina st. 4, Moscow, Russia, 119334

    Daniil G. Ivanov, Maria I. Indeykina, Adel E. Iusupov & Anna E. Bugrova

  2. Moscow Institute of Physics and Technology, Institutskiy pr.9, Dolgoprudny, Moscow Region, Russia, 141700

    Daniil G. Ivanov, Maria I. Indeykina, Stanislav I. Pekov, Adel E. Iusupov, Alexey S. Kononikhin & Igor A. Popov

  3. V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Center of Chemical Physic, Russian Academy of Sciences, Moscow, Russia

    Stanislav I. Pekov & Igor A. Popov

  4. V. I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Healthcare of the Russian Federation, Akademika Oparina ul.4, Moscow, Russia, 117198

    Anna E. Bugrova & Igor A. Popov

  5. Skolkovo Institute of Science and Technology, Novaya st. 100, Skolkovo, Moscow Region, Russia, 143025

    Alexey S. Kononikhin & Eugene N. Nikolaev

Authors
  1. Daniil G. Ivanov
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  2. Maria I. Indeykina
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  3. Stanislav I. Pekov
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  4. Adel E. Iusupov
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  5. Anna E. Bugrova
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  6. Alexey S. Kononikhin
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  7. Eugene N. Nikolaev
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  8. Igor A. Popov
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Correspondence to Eugene N. Nikolaev.

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Ivanov, D.G., Indeykina, M.I., Pekov, S.I. et al. Probabilistic model applied to ion abundances in product-ion spectra: quantitative analysis of aspartic acid isomerization in peptides. Anal Bioanal Chem 411, 7783–7789 (2019). https://doi.org/10.1007/s00216-019-02174-6

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  • DOI: https://doi.org/10.1007/s00216-019-02174-6

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