Biological and Medicinal Chemistry

Predicting the Shapes of Protein Complexes Through Collision Cross Section Measurements and Database Searches


In structural biology, collision cross sections (CCS) from ion mobility mass spectrometry (IM-MS) measurements are routinely compared to computationally or experimentally derived protein structures. Here, we investigate whether CCS data can inform about the shape of a protein in the absence of specific reference structures. Analysis of the proteins in the CCS database shows that protein complexes with low apparent densities are structurally more diverse than those with a high apparent density. Using the CCS, molecular weight, and oligomeric states to mine the Protein Data Bank (PDB) for potentially similar protein structures, we find that we can distinguish oblate- and prolate-shaped protein complexes. We then apply the strategy to an integral membrane protein by comparing the shapes of a prokaryotic and an eukaryotic sodium/proton antiporter homologue. We conclude that mining the PDB with IM-MS data is a time-effective way to derive low-resolution structural models.

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Submitted manuscript with journal-specific information and grant details removed.


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Supplementary material

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Supplementary Tables 1-4