Category: Featured

Molecular Insights into the Thermal Stability of mAbs with Variable-Temperature Ion-Mobility Mass Spectrometry

The aggregation of protein-based therapeutics such as monoclonal antibodies (mAbs) can affect the efficacy of the treatment and can even induce effects that are adverse to the patient. Protein engineering is used to shift the mAb away from an aggregation-prone state by increasing the thermodynamic stability of the native fold, which might in turn alter …

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Distinguishing Loss of Structure from Subunit Dissociation for Protein Complexes with Variable Temperature Ion Mobility Mass Spectrometry

Proteins and protein complexes undergo structural changes depending on the surrounding environment, in turn affecting their biological function.  Here, VT-MS is applied to study four multimeric protein complexes and allow for decoupling of their melting temperature (Tm) from the protein complex dissociation temperature (TGPD).   VT-IM-MS is used to investigate structural changes of these proteins at …

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Signature dynamics of intact immunoglobulin G revealed by drift-tube ion-mobility mass spectrometry and molecular modeling

Monoclonal antibodies (mAb) are a rapidly growing group of biopharmaceuticals.  Due to their intrinsic flexibility, intact mAbs provide a challenge with regards to higher order structure characterization.  Intact mAbs and their fragments are explored here using the DT-IM-MS and were found to be far more dynamic in the gas-phase than proteins of comparable size.  This …

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Insights into the Conformations of Three Structurally Diverse Proteins: Cytochrome c, p53, and MDM2, Provided by Variable-Temperature Ion Mobility Mass Spectrometry

Thermally induced conformational transitions of three proteins of increasing intrinsic disorder—cytochrome c, the tumor suppressor protein p53 DNA binding domain (p53 DBD), and the N-terminus of the oncoprotein murine double minute 2 (NT-MDM2)—have been studied by native mass spectrometry and variable-temperature drift time ion mobility mass spectrometry (VT-DT-IM-MS). Ion mobility measurements were carried out at temperatures …

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The use of ion mobility mass spectrometry to probe modulation of the structure of p53 and of MDM2 by small molecule inhibitors

Developing drug-like molecules to inhibit the interactions formed by disordered proteins is desirable due to the high correlation of disorder with protein implicated in disease, but is challenging due in part to the lack of atomistically resolved and resolvable structures from conformationally dynamic systems. Ion mobility mass spectrometry (IM-MS) is well-positioned to assess protein ligand …

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