Abstract
Electron transfer dissociation (ETD) is a versatile technique used in mass spectrometry for the high-throughput characterization of proteins. It consists of several competing reactions triggered by the transfer of an electron from its anion source to the sample cations. One can retrieve relative quantities of the products from mass spectra.
We present a method to analyze these results from the perspective of the reaction kinetics. A formal mathematical model of the ETD process is introduced and parametrized by intensities of the occurring reactions. Also, we introduce a method to estimate the reaction intensities by solving a nonlinear optimization problem. The presented method proves highly robust to noise on in silico generated data. Moreover, the presented model can explain a considerable amount of experimental results obtained under various experimental settings.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Syka, J.E.P., Coon, J.J., Schroeder, M.J., Shabanowitz, J., Hunt, D.F.: Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc. Natl. Acad. Sci. USA 101(26), 9528–9533 (2004)
Zhurov, K.O., Fornelli, L., Wodrich, M.D., Laskay, Ü.A., Tsybin, Y.O.: Principles of electron capture and transfer dissociation mass spectrometry applied to peptide and protein structure analysis. Chem. Soc. Rev. 42(12), 5014–5030 (2013)
Sohn, C.H., Chung, C.K., Yin, S., Ramachandran, P., Loo, J.A., Beauchamp, J.L.: Probing the mechanism of electron capture and electron transfer dissociation using tags with variable electron affinity. J. Am. Chem. Soc. 131(15), 5444–5459 (2009)
Sohn, C.H., Yin, S., Peng, I., Loo, J.A., Beauchamp, J.L.: Investigation of the mechanism of electron capture and electron transfer dissociation of peptides with a covalently attached free radical hydrogen atom scavenger. Int. J. Mass Spectrom. 390, 49–55 (2015)
Mitchell Wells, J., McLuckey, S.A.: Collision induced dissociation (CID) of peptides and proteins. In: Methods in Enzymology, pp. 148–185 (2005)
Kim, M.S., Pandey, A.: Electron transfer dissociation mass spectrometry in proteomics. Proteomics 12(4–5), 530–542 (2012)
Zhang, Z.: Prediction of low-energy collision-induced dissociation spectra of peptides. Anal. Chem. 76(14), 3908–3922 (2004)
Zhang, Z.: Prediction of low-energy collision-induced dissociation spectra of peptides with three or more charges. Anal. Chem. 77(19), 6364–6373 (2005)
Wysocki, V.H., Tsaprailis, G., Smith, L.L., Breci, L.A.: Mobile and localized protons: a framework for understanding peptide dissociation. J. Mass Spectrom. 35(12), 1399–1406 (2000)
Fenn, J., Mann, M., Meng, C., Wong, S., Whitehouse, C.: Electrospray ionization for mass spectrometry of large biomolecules. Science 246(4926), 64–71 (1989)
Lermyte, F., Konijnenberg, A., Williams, J., Brown, J., Valkenborg, D., Sobott, F.: ETD allows for native surface mapping of a 150 kDa noncovalent complex on a commercial Q-TWIMS-TOF instrument. J. Am. Soc. Mass Spectrom. 25(3), 343–350 (2014)
Lermyte, F., Sobott, F.: Electron transfer dissociation provides higher-order structural information of native and partially unfolded protein complexes. Proteomics 15(16), 2813–2822 (2015)
Lermyte, F., Łącki, M.K., Valkenborg, D., Baggerman, G., Gambin, A., Sobott, F.: Understanding reaction pathways in top-down ETD by dissecting isotope distributions: a mammoth task. Int. J. Mass Spectrom. 390, 146–154 (2015)
Lermyte, F., Williams, J.P., Brown, J.M., Martin, E.M., Sobott, F.: Extensive charge reduction and dissociation of intact protein complexes following electron transfer on a quadrupole-ion mobility-time-of-flight MS. J. Am. Soc. Mass Spectrom. 26(7), 1068–1076 (2015)
Li, W., Song, C., Bailey, D.J., Tseng, G.C., Coon, J.J., Wysocki, V.H.: Statistical analysis of electron transfer dissociation pairwise fragmentation patterns. Anal. Chem. 83(24), 9540–9545 (2011)
Breuker, K., Oh, H., Lin, C., Carpenter, B.K., McLafferty, F.W.: Nonergodic and conformational control of the electron capture dissociation of protein cations. Proc. Natl. Acad. Sci. USA 101(39), 14011–14016 (2004)
Simons, J.: Mechanisms for S-S and \(N-C_\alpha \) bond cleavage in peptide ECD and ETD mass spectrometry. Chem. Phys. Lett. 484(4–6), 81–95 (2010)
Tureček, F., Julian, R.R.: Peptide radicals and cation radicals in the gas phase. Chem. Rev. 113(8), 6691–6733 (2013)
Zhang, Z.: Prediction of electron-transfer/capture dissociation spectra of peptides. Anal. Chem. 82(5), 1990–2005 (2010)
Elias, J.E., Gibbons, F.D., King, O.D., Roth, F.P., Gygi, S.P.: Intensity-based protein identification by machine learning from a library of tandem mass spectra. Nat. Biotechnol. 22(2), 214–219 (2004)
Arnold, R.J., Jayasankar, N., Aggarwal, D., Tang, H., Radivojac, P.: A machine learning approach to predicting peptide fragmentation spectra. In: Pacific Symposium on Biocomputing, pp. 219–230 (2006)
Degroeve, S., Martens, L., Jurisica, I.: MS2PIP: a tool for MS/MS peak intensity prediction. Bioinformatics 29(24), 3199–3203 (2013)
Gambin, A., Kluge, B.: Modeling proteolysis from mass spectrometry proteomic data. Fund. Inform. 103(1–4), 89–104 (2010)
Lermyte, F., Łącki, M.K., Valkenborg, D., Gambin, A., Sobott, F.: Conformational space and stability of ETD charge reduction products of ubiquitin. J. Am. Soc. Mass Spectrom. 28(1), 69–76 (2017)
McLuckey, S.A., Stephenson, J.L.: Ion/ion chemistry of high-mass multiply charged ions. Mass Spectrom. Rev. 17(6), 369–407 (1999)
Gillespie, D.T.: Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 81(25), 2340–2361 (1977)
Lermyte, F., Verschueren, T., Brown, J.M., Williams, J.P., Valkenborg, D., Sobott, F.: Characterization of top-down ETD in a travelling-wave ion guide. Methods 89, 22–29 (2015)
Morrison, L.J., Brodbelt, J.S.: Charge site assignment in native proteins by ultraviolet photodissociation (UVPD) mass spectrometry. Analyst 141(1), 166–176 (2016)
Acknowledgements
This work was partially supported by the National Science Centre grants number 2013/09/B/ST6/01575, 2014/12/W/ST5/00592 and 2015/17/N/ST6/03565, the SBO grant InSPECtor (120025) of the Flemish agency for Innovation by Science and Technology (IWT). The authors thank the Research Foundation – Flanders (FWO) for funding a Ph.D. fellowship (F.L.). The Synapt G2 mass spectrometer is funded by a grant from the Hercules Foundation – Flanders.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this paper
Cite this paper
Ciach, M.A. et al. (2017). Estimation of Rates of Reactions Triggered by Electron Transfer in Top-Down Mass Spectrometry. In: Cai, Z., Daescu, O., Li, M. (eds) Bioinformatics Research and Applications. ISBRA 2017. Lecture Notes in Computer Science(), vol 10330. Springer, Cham. https://doi.org/10.1007/978-3-319-59575-7_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-59575-7_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-59574-0
Online ISBN: 978-3-319-59575-7
eBook Packages: Computer ScienceComputer Science (R0)