ANTIPASTI: interpretable prediction of antibody binding affinity exploiting normal modes and deep learning
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Published version
Author(s)
Michalewicz, Kevin
Barahona, Mauricio
Bravi, Barbara
Type
Journal Article
Abstract
The high binding affinity of antibodies towards their cognate targets is key to eliciting effective immune responses, as well as to the use of antibodies as research and therapeutic tools. Here, we propose ANTIPASTI, a Convolutional Neural Network model that achieves state-of-the-art performance in the prediction of antibody binding affinity using as input a representation of antibody-antigen structures in terms of Normal Mode correlation maps derived from Elastic Network Models. This representation captures not only structural features but energetic patterns of local and global residue fluctuations. The learnt representations are interpretable: they reveal similarities of binding patterns among antibodies targeting the same antigen type, and can be used to quantify the importance of antibody regions contributing to binding affinity. Our results show the importance of the antigen imprint in the Normal Mode landscape, and the dominance of cooperative effects and long-range correlations between antibody regions to determine binding affinity.
Date Issued
2024-12-05
Date Acceptance
2024-10-01
Citation
Structure, 2024, 32 (12), pp.2422-2434.e5
ISSN
0969-2126
Publisher
Elsevier
Start Page
2422
End Page
2434.e5
Journal / Book Title
Structure
Volume
32
Issue
12
Copyright Statement
© 2024 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
https://www.sciencedirect.com/science/article/pii/S0969212624004362?via%3Dihub
Publication Status
Published
Date Publish Online
2024-10-25