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.
%0 Journal Article
%1 Tran2022-mb
%A Tran, Minh H
%A Schoeder, Clara T
%A Schey, Kevin L
%A Meiler, Jens
%D 2022
%I Frontiers Media SA
%J Front. Immunol.
%K (HDX-MS); antibody-antigen biology; docking; epitope-paratope exchange hydrogen-deuterium identification; integrative interaction; mass modeling protein-protein spectrometry structural structure
%P 859964
%T Computational structure prediction for antibody-antigen complexes from hydrogen-deuterium exchange mass spectrometry: Challenges and outlook
%V 13
%X 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.
@article{Tran2022-mb,
abstract = {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.},
added-at = {2024-10-02T10:38:17.000+0200},
author = {Tran, Minh H and Schoeder, Clara T and Schey, Kevin L and Meiler, Jens},
biburl = {https://puma.scadsai.uni-leipzig.de/bibtex/2b089c854f710024e6092c685ce3d6d33/scadsfct},
copyright = {https://creativecommons.org/licenses/by/4.0/},
interhash = {3bc3de98dba51187c09e378caa08dc6e},
intrahash = {b089c854f710024e6092c685ce3d6d33},
journal = {Front. Immunol.},
keywords = {(HDX-MS); antibody-antigen biology; docking; epitope-paratope exchange hydrogen-deuterium identification; integrative interaction; mass modeling protein-protein spectrometry structural structure},
language = {en},
month = may,
pages = 859964,
publisher = {Frontiers Media SA},
timestamp = {2024-10-02T10:38:17.000+0200},
title = {Computational structure prediction for antibody-antigen complexes from hydrogen-deuterium exchange mass spectrometry: Challenges and outlook},
volume = 13,
year = 2022
}
