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Linking Gas-Phase and Solution-Phase Protein Unfolding via Mobile Proton Simulations.
Eldrid, Charles; Cragnolini, Tristan; Ben-Younis, Aisha; Zou, Junjie; Raleigh, Daniel P; Thalassinos, Konstantinos.
Affiliation
  • Eldrid C; School of Biological Sciences, University of Southampton, SouthamptonSO16 1BJ, U.K.
  • Cragnolini T; Institute of Structural and Molecular Biology, Division of Bioscience, University College London, LondonWC1E 6BT, U.K.
  • Ben-Younis A; Institute of Structural and Molecular Biology, Birkbeck College, University of London, LondonWC1E 7HX, U.K.
  • Zou J; Institute of Structural and Molecular Biology, Division of Bioscience, University College London, LondonWC1E 6BT, U.K.
  • Raleigh DP; Department of Chemistry, Stony Brook University, 100 Nicolls Rd., Stony Brook, New York11794, United States.
  • Thalassinos K; Institute of Structural and Molecular Biology, Division of Bioscience, University College London, LondonWC1E 6BT, U.K.
Anal Chem ; 94(46): 16113-16121, 2022 11 22.
Article de En | MEDLINE | ID: mdl-36350278
ABSTRACT
Native mass spectrometry coupled to ion mobility (IM-MS) combined with collisional activation (CA) of ions in the gas phase (in vacuo) is an important method for the study of protein unfolding. It has advantages over classical biophysical and structural techniques as it can be used to analyze small volumes of low-concentration heterogeneous mixtures while maintaining solution-like behavior and does not require labeling with fluorescent or other probes. It is unclear, however, whether the unfolding observed during collision activation experiments mirrors solution-phase unfolding. To bridge the gap between in vacuo and in-solution behavior, we use unbiased molecular dynamics (MD) to create in silico models of in vacuo unfolding of a well-studied protein, the N-terminal domain of ribosomal L9 (NTL9) protein. We utilize a mobile proton algorithm (MPA) to create 100 thermally unfolded and coulombically unfolded in silico models for observed charge states of NTL9. The unfolding behavior in silico replicates the behavior in-solution and is in line with the in vacuo observations; however, the theoretical collision cross section (CCS) of the in silico models was lower compared to that of the in vacuo data, which may reflect reduced sampling.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protons / Dépliement des protéines Langue: En Journal: Anal Chem Année: 2022 Type de document: Article Pays d'affiliation: Royaume-Uni

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protons / Dépliement des protéines Langue: En Journal: Anal Chem Année: 2022 Type de document: Article Pays d'affiliation: Royaume-Uni