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Two-dimensional partial covariance mass spectrometry for the top-down analysis of intact proteins.

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Title: Two-dimensional partial covariance mass spectrometry for the top-down analysis of intact proteins.
Authors: Driver, T
Averbukh, V
Frasiński, LJ
Marangos, JP
Edelson-Averbukh, M
Item Type: Journal Article
Abstract: Two-dimensional partial covariance mass spectrometry (2D-PC-MS) exploits the inherent fluctuations of fragment ion abundances across a series of tandem mass spectra, to identify correlated pairs of fragment ions produced along the same fragmentation pathway of the same parent (e.g., peptide) ion. Here, we apply 2D-PC-MS to the analysis of intact protein ions in a standard linear ion trap mass analyzer, using the fact that the fragment-fragment correlation signals are much more specific to the biomolecular sequence than one-dimensional (1D) tandem mass spectrometry (MS/MS) signals at the same mass accuracy and resolution. We show that from the distribution of signals on a 2D-PC-MS map it is possible to extract the charge state of both parent and fragment ions without resolving the isotopic envelope. Furthermore, the 2D map of fragment-fragment correlations naturally separates the products of the primary decomposition pathways of the molecular ions from those of the secondary ones. We access this spectral information using an adapted version of the Hough transform. We demonstrate the successful identification of highly charged, intact protein molecules bypassing the need for high mass resolution. Using this technique, we also perform the in silico deconvolution of the overlapping fragment ion signals from two co-isolated and co-fragmented intact proteins, demonstrating a viable new method for the concurrent mass spectrometric identification of a mixture of intact protein ions from the same fragment ion spectrum.
Issue Date: 10-Aug-2021
Date of Acceptance: 8-Jul-2021
URI: http://hdl.handle.net/10044/1/90619
DOI: 10.1021/acs.analchem.1c00332
ISSN: 0003-2700
Publisher: American Chemical Society
Start Page: 10779
End Page: 10788
Journal / Book Title: Analytical Chemistry
Volume: 93
Issue: 31
Copyright Statement: © 2021 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.analchem.1c00332
Sponsor/Funder: Wellcome Trust
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (E
Engineering & Physical Science Research Council (EPSRC)
Funder's Grant Number: 100093/Z/12/Z
GR/S22400/01
EP/I032517/1
EP/K503733/1
EP/N018680/1
Keywords: physics.chem-ph
physics.chem-ph
q-bio.BM
0301 Analytical Chemistry
0399 Other Chemical Sciences
Analytical Chemistry
Publication Status: Published
Conference Place: United States
Embargo Date: 2022-07-25
Online Publication Date: 2021-07-26
Appears in Collections:Quantum Optics and Laser Science
Physics
Faculty of Natural Sciences