Ensemble Methods Enable a New Definition for the Solution to Gas-Phase Transfer of Intrinsically Disordered Proteins.

TitleEnsemble Methods Enable a New Definition for the Solution to Gas-Phase Transfer of Intrinsically Disordered Proteins.
Publication TypeJournal Article
Year of Publication2015
AuthorsBorysik, A. J., Kovacs D., Guharoy M., and Tompa P.
JournalJ Am Chem Soc
Volume137
Issue43
Pagination13807-17
Date Published2015 Nov 04
ISSN1520-5126
KeywordsGases, Humans, Intrinsically Disordered Proteins, Molecular Dynamics Simulation, Phase Transition, Protein Conformation, Solutions, Spectrometry, Mass, Electrospray Ionization
Abstract

Intrinsically disordered proteins (IDPs) are important for health and disease, yet their lack of net structure precludes an understanding of their function using classical methods. Gas-phase techniques provide a promising alternative to access information on the structure and dynamics of IDPs, but the fidelity to which these methods reflect the solution conformations of these proteins has been difficult to ascertain. Here we use state of the art ensemble techniques to investigate the solution to gas-phase transfer of a range of different IDPs. We show that IDPs undergo a vast conformational space expansion in the absence of solvent to sample a conformational space 3-5 fold broader than in solution. Moreover, we show that this process is coupled to the electrospray ionization process, which brings about the generation of additional subpopulations for these proteins not observed in solution due to competing effects on protein charge and shape. Ensemble methods have permitted a new definition of the solution to gas-phase transfer of IDPs and provide a roadmap for future investigations into flexible systems by mass spectrometry.

DOI10.1021/jacs.5b06027
Alternate JournalJ. Am. Chem. Soc.
PubMed ID26437245
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