title: Ensemble Methods Enable a New Definition for the Solution to Gas-Phase Transfer of Intrinsically Disordered Proteins.
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.
authors.affiliation: King's College London , Department of Chemistry, Britannia House, 7 Trinity Street, London SE1 1DB, U.K.
authors.forename: Antoni J
authors.initials: AJ
authors.lastname: Borysik
authors.affiliation: VIB Structural Biology Research Centre (SBRC), Vrije Universiteit Brussel , Pleinlaan 2, Brussels B-1050, Belgium.
authors.forename: Denes
authors.initials: D
authors.lastname: Kovacs
authors.affiliation: VIB Structural Biology Research Centre (SBRC), Vrije Universiteit Brussel , Pleinlaan 2, Brussels B-1050, Belgium.
authors.forename: Mainak
authors.initials: M
authors.lastname: Guharoy
authors.affiliation: VIB Structural Biology Research Centre (SBRC), Vrije Universiteit Brussel , Pleinlaan 2, Brussels B-1050, Belgium.|Institute of Enzymology, Research Centre for Natural Sciences of the Hungarian Academy of Sciences , 1117 Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Tompa
mesh_terms: D005740:Gases / Q000737:chemistry; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D044367:Phase Transition; D011487:Protein Conformation; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D005740:Gases; D064267:Intrinsically Disordered Proteins; D012996:Solutions