Figure 4.

Structural stability as a correlate with immunogenicity. (A) Mutations within neoepitopes lead to structural alterations across the peptide backbone, as illustrated with structural snapshots from the simulations of the mutant and WT Tnpo3.1 epitope bound to H-2K^d. (B) Summary of structural differences for highly DAI ranked nonamers. Differences were quantified by superimposing average peptide conformations from the molecular dynamics simulations and computing RMSDs for all common atoms. Green and red bars indicate epitopes that led to either positive or negative immunological responses, respectively. The yellow bar shows the results for control calculations for an immunogenic HBV core epitope. (alue for the HBV epitope is the average Cα RMSD relative to the starting coordinates. (C) The numbers in the legend give the mean RMSF for the all amino acids of each peptide; those at the right give the value for only the C-terminal α carbon. Mutated amino acids are indicated by lower case in the x-axis. Results for all nonamers are in Fig. S1. (D) Effects of mutations on the conformational stability of all nonamers, calculated as the difference between the mean RMSF of the mutant and the WT peptide. (E) Fluctuations at the peptide C-terminal ends and immunogenicity. The dashed vertical line shows the mean value for all mutant nonamers. The yellow bar shows the C-terminal stability of the HBV core epitope control. Error bars represent SEM.