Dynamic structural analysis-based epitope prediction of Exendin-4 in aqueous solution.

The study of epitopes has a broad range of applications in drug discovery, vaccine design, and immunotherapy. In this study, an epitope prediction method was developed based on the dynamic structure of protein antigens. Solvent accessible surface area, charge, and root mean square fluctuation were introduced as the key residue property parameters. The epitope prediction algorithm was established by constructing a three-parameter complex metrics of seven-peptide groups. The method was applied to predict the epitopes of Exendin-4, an effective antidiabetic drug. The epitopes of both the natural and C-terminal amidated forms of Exendin-4 were predicted and compared in their folded and intermediate states. In the folded state, the epitopes of natural Exendin-4 (His1-Phe6 and Asp9-Val19) were found to be nearly identical to the epitopes of C-terminal aminated Exendin-4 (His1-Thr7 and Asp9-Val19). In the intermediate state, however, the epitopes of natural Exendin-4 (His1-Gly4, Phe6 and Lys12-Arg20) covered fewer amino acids than the epitopes of C-terminal aminated Exendin-4 (His1-Gly4, Phe6, Asp9-Val19 and Trp25-Lys27). The comparison with the results from other prediction tools demonstrates the reliability of our predicted epitopes of Exendin-4.