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Collision induced unfolding of isolated proteins in the gas phase: past, present, and future
Open accessAbstract
Rapidly characterizing the three-dimensional structures of proteins and the multimeric machines they form remains one of the great challenges facing modern biological and medical sciences. Ion mobility-mass spectrometry based techniques are playing an expanding role in characterizing these functional complexes, especially in drug discovery and development workflows. Despite this expansion, ion mobility-mass spectrometry faces many challenges, especially in the context of detecting small differences in protein tertiary structure that bear functional consequences. Collision induced unfolding is an ion mobility-mass spectrometry method that enables the rapid differentiation of subtly-different protein isoforms based on their unfolding patterns and stabilities. In this review, we summarize the modern implementation of such gas-phase unfolding experiments and provide an overview of recent developments in both methods and applications.
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“In addition, collision-induced unfolding (CIU), i.e., increasing the internal energy of an ion prior to IM-MS analysis, allows concomitant study of conformational stability, providing more details than IM alone.”
From Higher-order structural characterisation of native proteins and complexes by top-down mass spectrometry (2020) · cites this paper as [26]
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Bergman, A. E., Makey, D. M., Villafuerte-Vega, R. C., Slaney, T. R., Chennamsetty, N., Chen, G., Tao, L., & Ruotolo, B. T. (2026) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.6c00275 · Cited by 1
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Fe-S cluster biosynthesis and maturation: Mass spectrometry-based methods advancing the field
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Let’s get biophysical – How to get your favorite protein’s digits
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Experimental Evidence for Phosphorylation-Driven Allosteric Regulation of Alpha Synuclein FunctionPreprint
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Ion Mobility-Mass Spectrometry for Macromolecule Analysis
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Analytical applications of gas-phase ion chemistry enabled by mass spectrometry
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Native Top-Down Mass Spectrometry Links Structure and Gas-Phase Stability of ERα-LBD
Pathak, K., Fink, E. C., Brinkman, D., Nettles, K. W., Fanning, S. W., & Gomes, F. P. (2026) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.6c00287
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Kinetics of Collision-Induced Back-Isomerization of Photoisomer Ions
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Collision-Induced Conformational Changes of Trp-cage and Ubiquitin in the Gas Phase
Dubrovskii, S. A., & Balabaev, N. K. (2026) · Polymer Science Series A · doi:10.1134/s0965545x26600717
Collision Induced Unfolding Predicts the Aggregation of Glycoengineered Monoclonal Antibodies
Bergman, A. E., Armbruster, M. R., Makey, D. M., Rivera-Fuentes, N. A., Rangel-Angarita, V., Theobald, T., & Ruotolo, B. T. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c05321
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Metadata
- Authors
- Dixit, S. M., Polasky, D. A., & Ruotolo, B. T.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Ruotolo, Brandon T
- Venue
- Current Opinion in Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 42
- Pages
- 93-100
- ISSN
- 1367-5931 (ISSN-L)
- PMC
- PMC5828980
- OpenAlex
- W2772936471
- Cited by
- 235
- References
- 48
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 35 · 2023: 28 · 2022: 24 · 2021: 35 · 2020: 31 · 2019: 26 · 2018: 10
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 307 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Opinion in Chemical Biology (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (1253384)
- National Institutes of Health
- NIGMS (R01 GM095832)
- Eli Lilly and Company
- Agilent Technologies
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- collision-induced unfolding, ion mobility mass spectrometry, protein tertiary structure, protein isoforms, protein stability, protein complexes, drug discovery
- MeSH terms
- Ion Mobility Spectrometry, Biological Products, Gases, Protein Conformation, Proteins, Mass Spectrometry, Protein Structure, Secondary, Protein Isoforms, Drug Discovery, High-Throughput Screening Assays, Protein Unfolding
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