Exploring Conformational Landscapes Using Trap and Release Tandem Ion Mobility Spectrometry.

The dynamics and thermodynamics of structural changes in isolated glu-fibrinopeptide B (GluFib) were investigated by tandem ion mobility spectrometry (IMS). Doubly protonated GluFib ions were first selected by IMS and then stored for a controlled duration in a thermalized ion trap. Temperature-induced 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.