title: Combining ion mobility spectrometry with hydrogen-deuterium exchange and top-down MS for peptide ion structure analysis.
abstract: The gas-phase conformations of electrosprayed ions of the model peptide KKDDDDIIKIIK have been examined by ion mobility spectrometry (IMS) and hydrogen deuterium exchange (HDX)-tandem mass spectrometry (MS/MS) techniques. [M+4H](4+) ions exhibit two conformers with collision cross sections of 418 Å(2) and 471 Å(2). [M+3H](3+) ions exhibit a predominant conformer with a collision cross section of 340 Å(2) as well as an unresolved conformer (shoulder) with a collision cross section of ~367 Å(2). Maximum HDX levels for the more compact [M+4H](4+) ions and the compact and partially-folded [M+3H](3+) ions are ~12.9, ~15.5, and ~14.9, respectively. Ion structures obtained from molecular dynamics simulations (MDS) suggest that this ordering of HDX level results from increased charge-site/exchange-site density for the more compact ions of lower charge. Additionally, a new model that includes two distance calculations (charge site to carbonyl group and carbonyl group to exchange site) for the computer-generated structures is shown to better correlate to the experimentally determined per-residue deuterium uptake. Future comparisons of IMS-HDX-MS data with structures obtained from MDS are discussed with respect to novel experiments that will reveal the HDX rates of individual residues.
authors.affiliation: C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, 26506, USA.
authors.forename: Mahdiar
authors.initials: M
authors.lastname: Khakinejad
authors.forename: Samaneh Ghassabi
authors.initials: SG
authors.lastname: Kondalaji
authors.forename: Hossein
authors.initials: H
authors.lastname: Maleki
authors.forename: James R
authors.initials: JR
authors.lastname: Arndt
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Donohoe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Valentine
mesh_terms: D041961:Deuterium Exchange Measurement / Q000379:methods*; D007477:Ions / Q000032:analysis / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D007477:Ions; D010455:Peptides