B-Cell Epitope Discovery: The First Protein Flexibility-Based Algorithm – Zika Virus Conserved Epitope Demonstration

Antibody-antigen interaction – at antigenic local environments called B-cell epitopes – is a prominent mechanism for neutralization of infection. Effective mimicry, and display, of B-cell epitopes is key to vaccine design. Here, a physical approach is evaluated for the discovery of epitopes which evolve slowly over closely related pathogens (conserved epitopes). The approach is 1) protein flexibility-based and 2) demonstrated with the Zika virus, simulated via molecular dynamics. The approach is validated against 1) the seven structurally characterized flavivirus epitopes which have evolved the least (out of thirty-eight flavivirus-antibody structures) and 2) eight preexisting epitope and peptide discovery algorithms. For the first time, protein flexibility outperforms solvent accessible surface area as an epitope discovery metric.