The effect of different disulfide connectivity patterns on hepcidin structure: Investigated by molecular dynamics simulation.

Peptide therapeutic plays an important role in the high selectivity of biological agents and the manageability of small drugs. Hepcidin has been proven to be a major regulator of iron homeostasis in vertebrates. Molecular dynamics simulation was performed to investigate the effects of different disulfide connectivity patterns on the structure of hepcidin. The potential energies of 105 isomers were calculated, which can provide a reference for future work. In addition to validate the known disulfide connectivity pattern of hepcidin (Cys1-Cys8, Cys3-Cys6, Cys2-Cys4 and Cys5-Cys7, P95), two other possible patterns are being proposed: Cys1-Cys7, Cys2-Cys4, Cys3-Cys6, Cys5-Cys8 (P80); and Cys1-Cys6, Cys2-Cys5, Cys3-Cys4, with a disulfide bond between two adjacent cysteine moieties Cys7-Cys8 (P67). The present research provides a basis on understanding the structure/activity relationship of the protein complex interaction in other study. This will have important values in application of hepcidin and its homologues in medical diagnosis. [ABSTRACT FROM AUTHOR]