Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology

Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D. Alex Crowder, Morgan F. Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A. Tainer, Susan P. Lees-Miller and David C. Schriemer ()
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Frantisek Filandr: University of Calgary
Vladimir Sarpe: University of Calgary
Shaunak Raval: University of Calgary
D. Alex Crowder: University of Calgary
Morgan F. Khan: University of Calgary
Pauline Douglas: University of Calgary
Stephen Coales: Trajan Scientific & Medical - Raleigh
Rosa Viner: Thermo Fisher Scientific
Aleem Syed: Dana-Farber Cancer Institute, Harvard Medical School
John A. Tainer: The University of Texas MD Anderson Cancer Center
Susan P. Lees-Miller: University of Calgary
David C. Schriemer: University of Calgary

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract We present a hydrogen/deuterium exchange workflow coupled to tandem mass spectrometry (HX-MS2) that supports the acquisition of peptide fragment ions alongside their peptide precursors. The approach enables true auto-curation of HX data by mining a rich set of deuterated fragments, generated by collisional-induced dissociation (CID), to simultaneously confirm the peptide ID and authenticate MS1-based deuteration calculations. The high redundancy provided by the fragments supports a confidence assessment of deuterium calculations using a combinatorial strategy. The approach requires data-independent acquisition (DIA) methods that are available on most MS platforms, making the switch to HX-MS2 straightforward. Importantly, we find that HX-DIA enables a proteomics-grade approach and wide-spread applications. Considerable time is saved through auto-curation and complex samples can now be characterized and at higher throughput. We illustrate these advantages in a drug binding analysis of the ultra-large protein kinase DNA-PKcs, isolated directly from mammalian cells.

Date: 2024
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DOI: 10.1038/s41467-024-46610-3

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