Antibody CDR-H3 loop flexibility: Insights from X-ray crystallography, structural bioinformatics, and the limits of current deep learning methods
Abstract
Complementarity Determining Regions (CDRs) in antibodies, and in particular the CDR-H3 loop, often display conformational plasticity that is essential for their function. Due to this flexibility, the structural investigation of antibody-antigen binding cannot exclusively rely on experimental techniques that only provide snapshots of unbound and bound states, such as X-ray crystallography. Moreover, X-ray structures can be biased due to experimental conditions and crystal packing. In this context, computational techniques, and especially conformational sampling methods, are an essential complement to experiments. This work illustrates the interest of such a coupling of methods on the structural investigation of an anti-FGFR4 (Fibroblast growth factor receptor 4) antibody. X-ray crystallography experiments revealed a very significant conformational change of the CDR-H3 loop between unbound and bound states. Structural bioinformatics methods were then applied to provide a more global picture of the conformational space of this loop, and to confirm that the observed
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BibTeX
@article{barozet2026antibody,
title = {{Antibody CDR-H3 loop flexibility: Insights from X-ray crystallography, structural bioinformatics, and the limits of current deep learning methods}},
author = {Amélie Barozet and Magali Mathieu and David Papin and Béatrice Cameron and Tarik Dabdoubi and Anne Séverac and Paul Ferrari and Thierry Siméon and Marc Bianciotto and Juan Cortés},
journal = {Journal of Structural Biology},
year = {2026},
month = sep,
doi = {10.1016/j.jsb.2026.108368},
url = {https://laas.hal.science/hal-05752121v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antibody CDR-H3 loop flexibility: Insights from X-ray crystallography, structural bioinformatics, and the limits of current deep learning methods
AU - Amélie Barozet
AU - Magali Mathieu
AU - David Papin
AU - Béatrice Cameron
AU - Tarik Dabdoubi
AU - Anne Séverac
AU - Paul Ferrari
AU - Thierry Siméon
AU - Marc Bianciotto
AU - Juan Cortés
PY - 2026
DA - 2026/09/12
JO - Journal of Structural Biology
DO - 10.1016/j.jsb.2026.108368
UR - https://laas.hal.science/hal-05752121v1
AB - Complementarity Determining Regions (CDRs) in antibodies, and in particular the CDR-H3 loop, often display conformational plasticity that is essential for their function. Due to this flexibility, the structural investigation of antibody-antigen binding cannot exclusively rely on experimental techniques that only provide snapshots of unbound and bound states, such as X-ray crystallography. Moreover, X-ray structures can be biased due to experimental conditions and crystal packing. In this context, computational techniques, and especially conformational sampling methods, are an essential complement to experiments. This work illustrates the interest of such a coupling of methods on the structural investigation of an anti-FGFR4 (Fibroblast growth factor receptor 4) antibody. X-ray crystallography experiments revealed a very significant conformational change of the CDR-H3 loop between unbound and bound states. Structural bioinformatics methods were then applied to provide a more global picture of the conformational space of this loop, and to confirm that the observed
SN - 1047-8477
SN - 1095-8657
ER -