{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T15:01:15Z","timestamp":1785942075285,"version":"3.56.0"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM130708"],"award-info":[{"award-number":["R01GM130708"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2140004"],"award-info":[{"award-number":["2140004"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2203513"],"award-info":[{"award-number":["2203513"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A detailed understanding of ion conformational dynamics over a range of temperatures and time scales remains a central challenge in structural mass spectrometry. We recently introduced SLIMPHONY, which is a traveling-wave ion mobility (IM) instrument built on structures for lossless ion manipulations (SLIM), and demonstrated proof-of-concept experiments for conformational landscapes observed through controlled kinetics (CLOCK). Here, we develop CLOCK as a quantitative framework for probing ion dynamics on submillisecond to second time scales. We apply CLOCK to native-like ions of 6+ ubiquitin and 7+ cytochrome c and show that both the guard electrode potential and the duration of activation independently control the resulting conformational distributions. We then combine ion trajectory simulations with statistical methods to estimate effective translational temperatures, providing a physically interpretable scale for comparing activation conditions and a mechanistic understanding of CLOCK. Applying this temperature calibration to CLOCK experiments reveals that 6+ ubiquitin and 7+ cytochrome c exhibit very distinct unfolding kinetics over a similar range of effective temperatures. Together, these results establish CLOCK as a quantitative, temperature-resolved, and time-resolved framework for probing ion conformational dynamics.<\/jats:p>","DOI":"10.1021\/jasms.6c00218","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:16:21Z","timestamp":1784639781000},"page":"2023-2032","source":"Crossref","is-referenced-by-count":0,"title":["Conformational Landscapes\nObserved through Controlled\nKinetics (CLOCK): Precise Control of Ion Temperatures from Submillisecond\nto Second Time Scales"],"prefix":"10.1021","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-2334","authenticated-orcid":true,"given":"AnneClaire","family":"Wageman","sequence":"first","affiliation":[{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98195"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3299-6637","authenticated-orcid":true,"given":"Yuan","family":"Feng","sequence":"additional","affiliation":[{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98195"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-4128","authenticated-orcid":true,"given":"Addison E.","family":"Roush","sequence":"additional","affiliation":[{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98195"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rilke L.K.","family":"Grimlund","sequence":"additional","affiliation":[{"name":"Carleton College , , , ,","place":["Northfield, Minnesota, United States, 55057"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-4973","authenticated-orcid":true,"given":"Matthew F.","family":"Bush","sequence":"additional","affiliation":[{"name":"University of Washington , , , ,","place":["Seattle, Washington, United States, 98195"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"7","key":"2026080510092552300_cit1","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/nprot.2008.78","article-title":"Ion Mobility\u2013Mass\nSpectrometry Analysis of Large Protein Complexes","volume":"3","author":"Ruotolo","year":"2008","journal-title":"Nat. Protoc."},{"issue":"22","key":"2026080510092552300_cit2","doi-asserted-by":"publisher","first-page":"9557","DOI":"10.1021\/ac1022953","article-title":"Collision Cross Sections of Proteins and Their Complexes:\nA Calibration Framework and Database for Gas-Phase Structural Biology","volume":"82","author":"Bush","year":"2010","journal-title":"Anal. Chem."},{"issue":"2","key":"2026080510092552300_cit3","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1021\/ac503715v","article-title":"Ion Mobility-Derived Collision Cross Section As an\nAdditional Measure for Lipid Fingerprinting and Identification","volume":"87","author":"Paglia","year":"2015","journal-title":"Anal. Chem."},{"issue":"7572","key":"2026080510092552300_cit4","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nature15388","article-title":"Identification of Carbohydrate\nAnomers Using Ion Mobility\u2013Mass Spectrometry","volume":"526","author":"Hofmann","year":"2015","journal-title":"Nature"},{"issue":"1","key":"2026080510092552300_cit5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1146\/annurev-anchem-091522-031329","article-title":"Enhancing the Depth\nof Analyses with Next-Generation Ion Mobility Experiments","volume":"16","author":"Zercher","year":"2023","journal-title":"Annu. Rev. Anal. Chem."},{"key":"2026080510092552300_cit6","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S0076-6879(05)02005-7","article-title":"Collision-Induced\nDissociation (CID) of Peptides and\nProteins","volume":"402","author":"Wells","year":"2005","journal-title":"Methods Enzymol."},{"issue":"20","key":"2026080510092552300_cit7","doi-asserted-by":"publisher","first-page":"12775","DOI":"10.1021\/acs.analchem.9b02331","article-title":"Degronomics:\nMapping\nthe Interacting Peptidome of a Ubiquitin Ligase Using an Integrative\nMass Spectrometry Strategy","volume":"91","author":"Canzani","year":"2019","journal-title":"Anal. Chem."},{"issue":"5","key":"2026080510092552300_cit8","doi-asserted-by":"publisher","first-page":"1876","DOI":"10.1002\/mas.21793","article-title":"Native Top-down Mass Spectrometry for Higher-Order\nStructural Characterization of Proteins and Complexes","volume":"42","author":"Liu","year":"2023","journal-title":"Mass Spectrom. Rev."},{"issue":"3","key":"2026080510092552300_cit9","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.jasms.2008.11.014","article-title":"Collisional\nActivation of Protein Complexes: Picking up the Pieces","volume":"20","author":"Benesch","year":"2009","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"4","key":"2026080510092552300_cit10","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1021\/ar400223t","article-title":"Surface Induced\nDissociation: Dissecting Noncovalent\nProtein Complexes in the Gas Phase","volume":"47","author":"Zhou","year":"2014","journal-title":"Acc. Chem.\nRes."},{"key":"2026080510092552300_cit11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.cbpa.2017.11.010","article-title":"Collision Induced Unfolding of Isolated\nProteins in the Gas Phase: Past, Present, and Future","volume":"42","author":"Dixit","year":"2018","journal-title":"Curr. Opin. Chem. Biol."},{"issue":"13","key":"2026080510092552300_cit12","doi-asserted-by":"publisher","first-page":"9079","DOI":"10.1021\/acs.analchem.0c01265","article-title":"Using SLIM-Based\nIMS-IMS Together with Cryogenic Infrared Spectroscopy for Glycan Analysis","volume":"92","author":"Bansal","year":"2020","journal-title":"Anal. Chem."},{"issue":"2","key":"2026080510092552300_cit13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1039\/D2AN01452A","article-title":"Performance\nEvaluation of In-Source Ion Activation Hardware for Collision-Induced\nUnfolding of Proteins and Protein Complexes on a Drift Tube Ion Mobility-Mass\nSpectrometer","volume":"148","author":"Gadkari","year":"2023","journal-title":"The Analyst"},{"issue":"1","key":"2026080510092552300_cit14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1146\/annurev.anchem.1.031207.113001","article-title":"Biomolecule Analysis\nby Ion Mobility Spectrometry","volume":"1","author":"Bohrer","year":"2008","journal-title":"Annu. Rev. 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Chem."},{"issue":"7","key":"2026080510092552300_cit18","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1007\/s13361-016-1397-x","article-title":"A Structures\nfor Lossless Ion Manipulations (SLIM)\nModule for Collision Induced Dissociation","volume":"27","author":"Webb","year":"2016","journal-title":"J.\nAm. Soc. Mass Spectrom."},{"issue":"1","key":"2026080510092552300_cit19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1021\/jasms.1c00273","article-title":"Collision-Induced\nUnfolding of Native-like Protein Ions Within a Trapped Ion Mobility\nSpectrometry Device","volume":"33","author":"Borotto","year":"2022","journal-title":"J. Am. Soc. 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Fragmentation of the 1-Bromonaphthalene Radical\nCation","volume":"104","author":"Laskin","year":"2000","journal-title":"J. Phys. Chem. A"},{"issue":"30","key":"2026080510092552300_cit26","doi-asserted-by":"publisher","first-page":"7178","DOI":"10.1021\/ja9609157","article-title":"Blackbody Infrared\nRadiative Dissociation of Bradykinin and Its Analogues: Energetics,\nDynamics, and Evidence for Salt-Bridge Structures in the Gas Phase","volume":"118","author":"Schnier","year":"1996","journal-title":"J. Am. Chem. Soc."},{"issue":"9","key":"2026080510092552300_cit27","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.1021\/acs.analchem.0c04520","article-title":"Exploring Conformational\nLandscapes Using Trap and Release Tandem Ion Mobility Spectrometry","volume":"93","author":"Le Fe\u0300vre","year":"2021","journal-title":"Anal. Chem."},{"issue":"17","key":"2026080510092552300_cit28","doi-asserted-by":"publisher","first-page":"9405","DOI":"10.1021\/acs.analchem.5c00560","article-title":"Back Isomerization\nKinetics of Molecular Photoswitches: Complementary Insights from Liquid\nChromatography and Ion Mobility Measurements","volume":"97","author":"Robert","year":"2025","journal-title":"Anal. Chem."},{"issue":"14","key":"2026080510092552300_cit29","doi-asserted-by":"publisher","first-page":"7527","DOI":"10.1021\/acs.analchem.7b01234","article-title":"Structural Dynamics\nof Native-Like\nIons in the Gas Phase: Results from Tandem Ion Mobility of Cytochrome c","volume":"89","author":"Allen","year":"2017","journal-title":"Anal. Chem."},{"issue":"25","key":"2026080510092552300_cit30","doi-asserted-by":"publisher","first-page":"9589","DOI":"10.1021\/acs.analchem.3c01222","article-title":"Are the\nGas-Phase Structures of Molecular Elephants Enduring or Ephemeral?\nResults from Time-Dependent, Tandem Ion Mobility","volume":"95","author":"Zercher","year":"2023","journal-title":"Anal. Chem."},{"key":"2026080510092552300_cit31","doi-asserted-by":"publisher","first-page":"11115","DOI":"10.1021\/jacs.3c12892","article-title":"Metastability\nof Protein Solution Structures in the Absence of a Solvent: Rugged\nEnergy Landscape and Glass-like Behavior","volume":"146","author":"Cropley","year":"2024","journal-title":"J.\nAm. Chem. Soc."},{"issue":"14","key":"2026080510092552300_cit32","doi-asserted-by":"publisher","first-page":"5775","DOI":"10.1021\/ac201509p","article-title":"Effective\nTemperature of Ions in\nTraveling Wave Ion Mobility Spectrometry","volume":"83","author":"Morsa","year":"2011","journal-title":"Anal.\nChem."},{"issue":"3","key":"2026080510092552300_cit33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s13361-011-0313-7","article-title":"How Hot Are Your Ions in TWAVE Ion\nMobility Spectrometry?","volume":"23","author":"Merenbloom","year":"2012","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"8","key":"2026080510092552300_cit34","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1007\/s13361-014-0909-9","article-title":"Fragmentation and Isomerization Due\nto Field Heating in Traveling Wave Ion Mobility Spectrometry","volume":"25","author":"Morsa","year":"2014","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"12","key":"2026080510092552300_cit35","doi-asserted-by":"publisher","first-page":"2054","DOI":"10.1007\/s13361-016-1479-9","article-title":"Radio-Frequency\n(Rf) Confinement in Ion Mobility Spectrometry:\nApparent Mobilities and Effective Temperatures","volume":"27","author":"Allen","year":"2016","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"18","key":"2026080510092552300_cit36","doi-asserted-by":"publisher","first-page":"9118","DOI":"10.1021\/acs.analchem.6b02089","article-title":"Analysis\nof Native-Like Ions Using\nStructures for Lossless Ion Manipulations","volume":"88","author":"Allen","year":"2016","journal-title":"Anal.\nChem."},{"issue":"6","key":"2026080510092552300_cit37","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1007\/s13361-019-02170-1","article-title":"Principles of Ion\nSelection, Alignment,\nand Focusing in Tandem Ion Mobility Implemented Using Structures for\nLossless Ion Manipulations (SLIM)","volume":"30","author":"Eaton","year":"2019","journal-title":"J. Am. Soc.\nMass Spectrom."},{"issue":"6","key":"2026080510092552300_cit38","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1021\/jasms.3c00112","article-title":"A Flexible, Modular\nPlatform for Multidimensional Ion Mobility of Native-like Ions","volume":"34","author":"Eaton","year":"2023","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"2026080510092552300_cit39","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ijms.2016.09.013","article-title":"Nonspecific Aggregation\nin Native Electrokinetic Nanoelectrospray Ionization","volume":"420","author":"Davidson","year":"2017","journal-title":"Int. J. Mass Spectrom."},{"key":"2026080510092552300_cit40","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1021\/jasms.5c00217","article-title":"SLIMPHONY:\nA SLIM-Based\nInstrument That Orchestrates Complex Ion Mobility\u2013Mass Spectrometry\nExperiments","volume":"37","author":"Wageman","year":"2026","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"5","key":"2026080510092552300_cit41","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/S1044-0305(02)00372-0","article-title":"Temperature-Dependent\nH\/D Exchange of Compact and Elongated\nCytochrome c Ions in the Gas Phase","volume":"13","author":"Valentine","year":"2002","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"35","key":"2026080510092552300_cit42","doi-asserted-by":"publisher","first-page":"12248","DOI":"10.1021\/acs.analchem.2c03066","article-title":"Protein Unfolding in\nFreeze Frames: Intermediate States Are Revealed by Variable-Temperature\nIon Mobility\u2013Mass Spectrometry","volume":"94","author":"Ujma","year":"2022","journal-title":"Anal.\nChem."},{"issue":"5","key":"2026080510092552300_cit43","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1021\/jasms.1c00364","article-title":"Effect of Traveling\nWaveform Profiles on Collision\nCross Section Measurements in Structures for Lossless Ion Manipulations","volume":"33","author":"Kwantwi-Barima","year":"2022","journal-title":"J. Am. Soc. Mass Spectrom."},{"issue":"16","key":"2026080510092552300_cit44","doi-asserted-by":"publisher","first-page":"6450","DOI":"10.1021\/acs.analchem.4c00692","article-title":"Altering Conformational\nStates of Dynamic Ion Populations\nUsing Traveling Wave Structures for Lossless Ion Manipulations","volume":"96","author":"Kinlein","year":"2024","journal-title":"Anal. Chem."},{"issue":"5","key":"2026080510092552300_cit45","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1021\/ac951038a","article-title":"Tandem\nMass Spectrometry of Large\nBiomolecule Ions by Blackbody Infrared Radiative Dissociation","volume":"68","author":"Price","year":"1996","journal-title":"Anal. 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Mass Spectrom."}],"container-title":["Journal of the American\nSociety for Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jasms.6c00218","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/8\/2023\/66084640\/jasms.6c00218.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jamsef\/article-pdf\/37\/8\/2023\/66084640\/jasms.6c00218.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:23:46Z","timestamp":1785939826000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jamsef\/article\/37\/8\/2023\/5224533\/Conformational-Landscapes-Observed-through"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,7,21]]},"published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1021\/jasms.6c00218","relation":{},"ISSN":["1044-0305","1879-1123"],"issn-type":[{"value":"1044-0305","type":"print"},{"value":"1879-1123","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}