The role of disulfide bonds and N‐terminus in the structural properties of hepcidins: Insights from molecular dynamics simulations

The main purpose of this work is to analyse, by means of molecular dynamics (MD) simulations both structural and mechanical‐dynamical differences between Hepcidin‐20 and Hepcidin‐25 in both oxidized and reduced states in aqueous solution. Results indicate that the presence of disulfide bonds is essential, in both peptides, for maintaining their β‐hairpin motif. As a matter of fact, the lack of this intra‐peptide covalent interactions produces an almost immediate deviation from the oxidized, plausibly active, structure in both the systems. Interestingly, reduced Hepcidin‐25 turns out to be characterized by a highly fluctuating structure which is found to rapidly span a large number of configurations at equilibrium. On the other hand, loss of disulfide bonds in the shorter peptide, results in a more compact and relatively rigid double‐turn structure. Comparison of mechanical–dynamical properties and sidechains–sidechains interactions in oxidized Hepcidin‐20 and Hepcidin‐25 strongly suggest also the key role of N‐terminus in the aggregation tendency of Hepcidin‐25. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 917–926, 2010.