ArticleJournal of the American Society for Mass Spectrometry2020
Using 10,000 Fragment Ions to Inform Scoring in Native Top-down Proteomics.
Article in Journal of the American Society for Mass Spectrometry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Improved Protein Identification in Native Ambient Mass Spectrometry by the Integration of Proton Transfer Charge Reduction and Higher-Energy Collision Dissociation (PTCR-HCD MS3).Journal of the American Society for Mass Spectrometry · 2026Article
- Native Top-Down Mass Spectrometry Combined with High-Resolution Charge Variant Analysis of Trastuzumab Originator and Biosimilars.Journal of the American Society for Mass Spectrometry · 2026Article
- On the Utility of Infrared Photoactivation for Native Top-Down and Complex-Down Orbitrap Mass Spectrometry of Soluble Proteoform Complexes.Journal of the American Society for Mass Spectrometry · 2026Article
- Integrated Native Mass Spectrometry Imaging of Soluble and Membrane Proteins.Journal of the American Chemical Society · 2026Article
- Imaging of Protein Assemblies up to 231 kDa in Tissues with Nano-DESI Mass Spectrometry.Analytical chemistry · 2025Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- Accessing Different Protein Conformer Ensembles with Tunable Capillary Vibrating Sharp-Edge Spray Ionization.The journal of physical chemistry. B · 2025Article
- Top-down mass spectrometry of native proteoforms and their complexes: a community study.Nature methods · 2024Article
- Panda-UV Unlocks Deeper Protein Characterization with Internal Fragments in Ultraviolet Photodissociation Mass Spectrometry.Analytical chemistry · 2024Article
- A High-Throughput Workflow for Mass Spectrometry Analysis of Nucleic Acids by Nanoflow Desalting.Analytical chemistry · 2024Article
- Infrared Multiphoton Dissociation Enables Top-Down Characterization of Membrane Protein Complexes and G Protein-Coupled Receptors.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Article
- Infrared Multiphoton Dissociation Enables Top-Down Characterization of Membrane Protein Complexes and G Protein-Coupled Receptors.Angewandte Chemie (International ed. in English) · 2023Article
- ProSight Native: Defining Protein Complex Composition from Native Top-Down Mass Spectrometry Data.Journal of proteome research · 2023Article
- Fragment Ion Abundance Reveals Information about Structure and Charge Localization in Highly Charged Proteins.Journal of the American Society for Mass Spectrometry · 2023Article
- Deciphering combinatorial post-translational modifications by top-down mass spectrometry.Current opinion in chemical biology · 2022Review
- Native Ambient Mass Spectrometry Enables Analysis of Intact Endogenous Protein Assemblies up to 145 kDa Directly from Tissue.Analytical chemistry · 2022Article
- Extending Native Top-Down Electron Capture Dissociation to MDa Immunoglobulin Complexes Provides Useful Sequence Tags Covering Their Critical Variable Complementarity-Determining Regions.Analytical chemistry · 2021Article
- Influence of Primary Structure on Fragmentation of Native-Like Proteins by Ultraviolet Photodissociation.Journal of the American Society for Mass Spectrometry · 2021Article
- Article
- Reassembling protein complexes after controlled disassembly by top-down mass spectrometry in native mode.International journal of mass spectrometry · 2021Article
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Authors and funding
10 authors.
Funding
Abstract
Protein fragmentation is a critical component of top-down proteomics, enabling gene-specific protein identification and full proteoform characterization. The factors that influence protein fragmentation include precursor charge, structure, and primary sequence, which have been explored extensively for collision-induced dissociation (CID). Recently, noticeable differences in CID-based fragmentation were reported for native versus denatured proteins, motivating the need for scoring metrics that are tailored specifically to native top-down mass spectrometry (nTDMS). To this end, position and intensity were tracked for 10,252 fragment ions produced by higher-energy collisional dissociation (HCD) of 159 native monomers and 70 complexes. We used published structural data to explore the relationship between fragmentation and protein topology and revealed that fragmentation events occur at a large range of relative residue solvent accessibility. Additionally, our analysis found that fragment ions at sites with an N-terminal aspartic acid or a C-terminal proline make up on average 40 and 27%, respectively, of the total matched fragment ion intensity in nTDMS. Percent intensity contributed by each amino acid was determined and converted into weights to (1) update the previously published C-score and (2) construct a native Fragmentation Propensity Score. Both scoring systems showed an improvement in protein identification or characterization in comparison to traditional methods and overall increased confidence in results with fewer matched fragment ions but with high probability nTDMS fragmentation patterns. Given the rise of nTDMS as a tool for structural mass spectrometry, we forward these scoring metrics as new methods to enhance analysis of nTDMS data.
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