Academic Journal
Rigorous Analysis of Multimodal HDX-MS Spectra.
| Τίτλος: | Rigorous Analysis of Multimodal HDX-MS Spectra. |
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| Συγγραφείς: | Tuttle LM; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States., James EI; Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States., Georgescauld F; Cell Signaling Technology, Danvers, Massachusetts 01923, United States., Wales TE; Department of Chemistry & Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Weis DD; Department of Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States., Engen JR; Department of Chemistry & Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Nath A; Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States., Klevit RE; Department of Biochemistry, University of Washington, Seattle, Washington 98195, United States., Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, United States. |
| Πηγή: | Journal of the American Society for Mass Spectrometry [J Am Soc Mass Spectrom] 2025 Feb 05; Vol. 36 (2), pp. 416-423. Date of Electronic Publication: 2025 Jan 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: ACS Publications Country of Publication: United States NLM ID: 9010412 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1123 (Electronic) Linking ISSN: 10440305 NLM ISO Abbreviation: J Am Soc Mass Spectrom Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : Washington, DC : ACS Publications Original Publication: New York, NY : Elsevier, c1990- |
| Ιατρικοί όροι (MeSH): | Proteins*/chemistry , Hydrogen Deuterium Exchange-Mass Spectrometry*/methods, Peptides/chemistry ; Algorithms ; Software |
| Περίληψη: | An inherent strength of hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) is its ability to detect the presence of multiple conformational states of a protein, which often manifest as multimodal isotopic envelopes. However, the statistical considerations for accurate analysis of multimodal spectra have yet to be established. Here we outline an unrestrained binomial distribution fitting approach with the corresponding statistical tests to accurately detect and, when possible, deconvolute isotopic distributions that contain multiple subpopulations. The algorithms have been incorporated into an updated version of the freely available software, HX-Express, and validated using known mixtures of peptides deuterated to varying degrees. This approach presents a readily accessible tool to fit and interpret bimodal and trimodal behavior in HDX-MS data for mixed populations, EX1 kinetics, and pulse labeling data. |
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| Grant Information: | R01 CA233978 United States CA NCI NIH HHS; R01 AI171570 United States AI NIAID NIH HHS; T32 GM007750 United States GM NIGMS NIH HHS; R01 EY017370 United States EY NEI NIH HHS; S10 OD030237 United States OD NIH HHS; R01 GM127579 United States GM NIGMS NIH HHS |
| Contributed Indexing: | Keywords: EX1; H/D exchange; HDX-MS; bimodal; deconvolution; deuterium; multimodal |
| Substance Nomenclature: | 0 (Proteins) 0 (Peptides) |
| Entry Date(s): | Date Created: 20250121 Date Completed: 20250502 Latest Revision: 20260206 |
| Update Code: | 20260206 |
| PubMed Central ID: | PMC12034455 |
| DOI: | 10.1021/jasms.4c00471 |
| PMID: | 39837577 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-1123 |
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| DOI: | 10.1021/jasms.4c00471 |