Evaluation of ion mobility spectroscopy for determining charge-solvated versus salt-bridge structures of protonated trimers

Abstract

The cross sections of five different protonated trimers consisting of two base molecules and trifluoroacetic acid were measured by using ion mobility spectrometry. The gas-phase basicities of these five base molecules span an 8-kcal/mol range. These cross sections are compared with those determined from candidate low-energy salt-bridge and charge-solvated structures identified by using molecular mechanics calculations using three different force fields: AMBER*, MMFF, and CHARMm. With AMBER*, the charge-solvated structures are all globular and the salt-bridge structures are all linear, whereas with CHARMm, these two forms of the protonated trimers can adopt either shape. Globular structures have smaller cross sections than linear structures. Conclusions about the structure of these protonated trimers are highly dependent on the force field used to generate low-energy candidate structures. With AMBER*, all of the trimers are consistent with salt-bridge structures, whereas with MMFF the measured cross sections are more consistent with charge-solvated structures, although the assignments are ambiguous for two of the protonated trimers. Conclusions based on structures generated by using CHARMm suggest a change in structure from charge-solvated to salt-bridge structures with increasing gas-phase basicity of the constituent bases, a result that is most consistent with structural conclusions based on blackbody infrared radiative dissociation experiments for these protonated trimers and theoretical calculations on the uncharged base-acid pairs. T he structure of a molecule in solution depends both on intramolecular interactions and on intermolecular interactions between the molecule and solvent. Gas-phase studies can provide information about the intrinsic properties of a molecule. From such measurements, information about solvent effects can be inferred. A number of different methods can provide information about molecular structure in the gas phase, even complex systems, such as large synthetic or biological polymers. These methods include spectroscopy [1][2][3][4][5], hydrogen/deuterium exchange [6-12], dissociation [13][14][15][16][17][18], proton transfer reactivity [19][20][21][22], and ion mobility mass spectrometry . These methods have been used to obtain information about protein conformation and folding, DNA duplex structure, and in a wide variety of other interesting applications.Of these methods, ion mobility mass spectrometry, a method pioneered by Bowers and Jarrold for ion structure characterization, has several advantages, including rapid measurement time, minimal perturbation of ground state structure, exquisite temperature control, and the ability to investigate kinetics of structural change over a limited time. With ion mobility, ions are injected into a drift tube where they thermalize through collisions with an introduced background gas, typically helium. In the presence of an applied electric field, ions are made to drift through an elevated pressure region. Based on the drift time through this tube...

Ion Mobility Analysis of Molecular Dynamics

“…As an example of the last, Jarrold and coworkers (29,30) showed that the addition of a charge on the carboxyl terminus stabilizes the helical macrodipole of polyalanine peptides in the gas phase. However, balancing charge solvation and Coulomb repulsion often dominates in smaller peptides (31)(32)(33)(34). Here, we focus on bradykinin (BK) (35,36) with the sequence RPPGFSPFR and specifically on its charge state +3.…”

Evidence for α-helices in the gas phase: A case study using Melittin from honey bee venom

“…Using molecular dynamics, Bern eche et al 12 determined that residue Lys-7 located in the hydrophobic moiety of the helix forms H-bonds with the hydrophilic end of lipid chains, anchoring the chain parallel to the bilayer. [19][20][21] An example of this latter class is shown in the work of Jarrold and co-workers, who examined a series of helix forming peptides using ion mobility mass spectrometry (IM-MS). Water molecules at the membrane interface cause disruption of the a-helix at the basic C-terminus.…”

“…These can be split into two distinguishable areas: the first to preserve and understand solution phase conformations and complex topology with careful use of native electrospray ionisation which consider systems of large molecular weight, [15][16][17][18] the second to determine intrinsic molecular interactions responsible for conformations adopted in the gas phase, often the latter is concerned with small model systems. [19][20][21] An example of this latter class is shown in the work of Jarrold and co-workers, who examined a series of helix forming peptides using ion mobility mass spectrometry (IM-MS). 22 By combining both theory and experiment, they found strong evidence for preservation of helices even at high temperatures.…”

Ion mobility resolved photo‐fragmentation to discriminate protomers

“…The emergence of soft ionization techniques, and then native mass spectrometry, has motivated the development of experimental strategies for the determination of the three‐dimensional structures of molecular, and especially biomolecular systems in the gas phase. A wealth of techniques have been proposed as gas‐phase structural probes, among which infrared multiphoton dissociation (IRMPD) and ion mobility spectrometry (IMS) have been the most widely used. The hierarchical structuration of biomolecules nevertheless renders the problem of structure determination particularly tricky to solve, thus justifying the combination of putatively complementary techniques.…”