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 b-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 Nterminus in the aggregation tendency of Hepcidin-25. # 2010 Wiley Periodicals, Inc. Biopolymers 00: 000–000,