Although computational structure prediction has had great successes in recent years, it
regularly fails to predict the interactions of large protein complexes with residue-level
accuracy, or even the correct orientation of the protein partners. The performance of
computational docking can be notably enhanced by incorporating experimental data from
structural biology techniques. A rapid method to probe protein-protein interactions is
hydrogen-deuterium exchange mass spectrometry (HDX-MS). HDX-MS has been
increasingly used for epitope-mapping of antibodies (Abs) to their respective antigens
(Ags) in the past few years. In this paper, we review the current state of HDX-MS in
studying protein interactions, specifically Ab-Ag interactions, and how it has been used to
inform computational structure prediction calculations. Particularly, we address the
limitations of HDX-MS in epitope mapping and techniques and protocols applied to
overcome these barriers. Furthermore, we explore computational methods that leverage
HDX-MS to aid structure prediction, including the computational simulation of HDX-MS
data and the combination of HDX-MS and protein docking. We point out challenges in
interpreting and incorporating HDX-MS data into Ab-Ag complex docking and highlight
the opportunities they provide to build towards a more optimized hybrid method, allowing
for more reliable, high throughput epitope identification.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:86430 |
| Date | 11 July 2023 |
| Creators | Tran, Minh H., Schoeder, Clara T., Schey, Kevin L., Meiler, Jens |
| Publisher | Frontiers Media |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 859964 |
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