title: The role of disulfide bonds and N-terminus in the structural properties of hepcidins: insights from molecular dynamics simulations.
abstract: 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 beta-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.
authors.affiliation: Dipartimento di Chimica, Ingegneria Chimica e Materiali, Universita' di L'Aquila, Via Vetoio s.n.c. Coppito (AQ), Italy. aschi@caspur.it
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
authors.forename: Argante
authors.initials: A
authors.lastname: Bozzi
authors.forename: Renato
authors.initials: R
authors.lastname: Di Bartolomeo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Petruzzelli
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D064451:Hepcidins; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; D004220:Disulfides; D064451:Hepcidins