Experimentally Observed Conformational Changes in Antibodies Due to Binding and Paratope-epitope Asymmetries.

Understanding binding related changes in antibody conformations is important for epitope prediction and antibody refinement. The increase of available data in the PDB allowed a more detailed investigation of the conformational landscape for free and bound antibodies. A dataset containing a total of 835 unique PDB entries of antibodies that were crystallized in complex with their antigen and in a free state was constructed. It was examined for binding related conformation changes. We present further evidence supporting the theory of a pre-existing-equilibrium in experimental data. Multiple sequence alignments did not show binding induced tendencies in the solvent accessibility of residues in any specific position. Evaluating the changes in solvent accessibility per residue revealed a certain binding induced increase for several amino acids. Antibody-antigen interaction statistics were established and quantify a significant directional asymmetry between many interacting antibody and antigen residue pairs, especially a richness in tyrosine in the antibody epitope compared to its paratope. This asymmetry could potentially facilitate an increase in the success rate of computationally guided antibody refinement.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)