Epitope rigidity and long-range coupling shape antigen dynamics in lysozyme-antibody complexes.

Conformational B-cell epitopes typically rigidify upon antibody binding, while distal antigen regions often become more flexible, yet the mechanistic basis remains unclear. Here we analyze 17 structurally similar lysozyme-antibody complexes using Anisotropic Network Models, Perturbation Response Scanning, and residue-level network analysis. We find that epitope residues are intrinsically low-mobility and act as dynamically influential sites in the unbound antigen, mechanically coupled to distant regions that increase flexibility upon binding. Normal mode analysis reveals that epitopes behave as rigid blocks within global motions, supporting their mechanically cohesive behavior within the antigen structure. These findings suggest that mobility redistribution upon antibody binding arises from pre-existing long-range dynamic coupling encoded in the antigen fold, providing a mechanistic framework linking epitope rigidity, allosteric communication, and global dynamical regulation in lysozyme-Fab complexes.