Exploring Conformational Landscapes Using Trap and Release Tandem Ion Mobility Spectrometry

Abstract

The dynamics and thermodynamics of structural changes in isolated glu-fibrinopeptide B (GluFib) were investigated by tandem ion mobility spectrometry (IMS). Doubly protonated GluFib 2+ ions were first selected by IMS and then stored for a controlled duration in a thermalized ion trap. Temperatureinduced conformational changes were finally monitored by IMS as a function of trapping time. Based on this procedure, isomerization rates and equilibrium populations of the different conformers were determined as a function of temperature. We demonstrate that the measured thermodynamic quantities can be directly compared to simulated observables from ensemble molecular modeling based on appropriate order parameters. We obtained good qualitative agreement with replica-exchange molecular dynamics simulations based on the AMOEBA force field and processed using the weighted histogram analysis method. This suggests that the balance between Coulomb repulsion and optimal charge solvation is the main source of the observed conformational bistability. Our results emphasize the differences between the kinetically driven quasi-equilibrium distributions obtained after collisional activation and the thermodynamically driven distributions from the present equilibrium experiments due to entropic effects. As a consequence, our measurements not only allow straightforward determination of Arrhenius activation energies but also yield the relative enthalpy and entropy changes associated to a structural transition.

Are the Gas-Phase Structures of Molecular Elephants Enduring or Ephemeral? Results from Time-Dependent, Tandem Ion Mobility

“…Although it is generally accepted that native-like ions can be generated from gentle ionization sources, , there has been a concerted experimental effort devoted to understanding the structural evolution of ions in the absence of solvent. IM–MS, time-dependent IM–MS, − time-dependent IM–IM–MS, − molecular dynamics simulations, − electron capture dissociation, , and hydrogen-deuterium exchange have been used to analyze the structures and stabilities of gas-phase ions. Relative to traditional, single-dimension IM, next-generation IM measurements require longer timescales, e.g., hundreds of milliseconds and longer, which provide additional opportunity for the properties of ions to change during measurements.…”

Exploring Isomerism in Isolated Cyclodextrin Oligomers through Trapped Ion Mobility Mass Spectrometry

“…Techniques like electron microscopy, nuclear magnetic resonance spectroscopy, or other spectroscopic methods mostly provide ensemble averaged structural information. By contrast, ion mobility mass spectrometry (IM MS) can provide information on the isomeric states of isolated monomers and of mass-selected and therefore size-selected oligomers. − …”

Structural and dynamical insights into SilE silver binding from combined analytical probes

“…22 However, no sign of such process was observed when selecting either of the population in a tandem-IMS scheme. 23 Consequently, the two observed peaks can be attributed to the existence of two distinct conformational families, either pre-existing in solution, or more likely resulting from structural reorganization upon desolvation. In the following, we focus on the relative intensity of the main Please do not adjust margins Please do not adjust margins two populations.…”