Ion Mobility-Mass Spectrometry: from Gas-Phase Thermochemistry of Biomolecular Ions to Native Structures
- Associate Professor Jim Prell, Chemistry, University of Oregon
- Journal club discussion of Determination of Thermochemical Barriers in Multiple-Collision-Induced Dissociation Experiments on Gas-Phase Protein Complexes. Tuesday, January 13, 9:00 – 10:00 am in BAG 192H. Moderated by Addison Roush.
- Journal club discussion of Gábor Transform-Based Antibody Quantitation in Serum: An Interlaboratory Liquid Chromatography/High-Resolution Mass Spectrometry Investigation. Tuesday, January 20, 9:00 – 10:00 am in BAG 192H. Moderated by Chris Weir.
- Seminar, followed by open discussion: Monday, January 26, 2022, 3:30 – 4:30 p.m. in BAG 260. Link
- Native ion mobility-mass spectrometry (IM-MS) aims to reveal structural information about biomolecules and their complexes, including and especially those that frustrate conventional techniques. One of the most common ways to access information beyond ion mass and charge in native IM-MS is to subject ions to hundreds to thousands of high-energy collisions with buffer gas, which can cause the ions to unfold (“Collision Induced Unfolding”, CIU) or dissociate (“Collision Induced Dissociation”, CID). Here, we apply our recently developed IonSPA software to determine thermochemical barriers encountered in CIU and CID of native protein ions. To date, CIU has been used largely to empirically characterize differences in structure between closely related proteins, such as innovator biologics and their biosimilars. A deeper view into biomolecular ion structure has been difficult to obtain with CIU in part due to the unclear relationship between the acceleration potential applied to the ions and their corresponding change in internal energy. We show that, with IonSPA, the internal energy (and temperature) of ions in CIU as a function of time can be straightforwardly modeled and used to determine enthalpy and entropy barriers for each unfolding step in the CIU “fingerprints” of several protein and protein complex ions. Recently, it has become possible to undertake molecular dynamics simulations capable of probing structural transitions relevant to the upper-microsecond unfolding timescale of the CIU experiments. We show how such simulations can help elucidate the relationship between unfolding enthalpy and entropy barriers of individual unfolding steps and the types of structural motif that are likely associated with them. The results are a major step toward direct inference of higher-order structural information about native biomolecules from a combination of gas-phase experimental and computational methods.
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