Kostas Thalassinos

Probing the Structure and Dynamics of Proteins by Means of Cyclic Ion Mobility Spectrometry and Electron Capture Dissociation

Kostas Thalassinos1

1. University College London

Modern protein prediction methods using deep neural networks can now achieve extremely accurate results when predicting protein structures from the protein’s sequence. Despite this impressive achievement these approaches still struggle to predict the structure of flexible proteins, and those where a single folded state does not represent the majority conformation.

By contrast, structural mass spectrometry approaches, and in particular ion mobility-mass spectrometry, can probe the dynamic conformational landscape of proteins and proteins in complex with other molecules.

Here we describe results using a travelling wave (TW) cyclic IM (cIM) device. The geometry of this instrument enables complex tandem IM experiments to be performed which were used to obtain more detailed collision induced unfolding pathways for the protein studied. In addition, we combined conformer selection with electron capture dissociation (ECD) in a single experiment to obtain a more in-depth characterisation of the different conformers. We used our multi-layered experimental approach to study proteins exhibiting multiple conformations, such as calmodulin, as well as proteins prone to misfolding and aggregation such as human islet amyloid polypeptide (hIAPP).

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