Is there a difference in metal ion-based inhibition between members of thionin family: Molecular dynamics simulation study Original Research Article

Thionins have a considerable potential as antimicrobial compounds although their application may be restricted by metal ion-based inhibition of membrane permeabilizing activity. We previously reported the properties associated with the proposed mechanism of metal ion-based inhibition of β-purothionin. In this study, we investigated the effects of metal ions on α-hordothionin which differs from β-purothionin by eight out of 45 residues. Three of the differing residues are thought to be involved in the mechanism of metal ion-based inhibition in β-purothionin. The structure and dynamics of α-hordothionin were explored using unconstrained molecular dynamics (MD) simulations in explicit water as a function of metal ions. Although the global fold is almost identical to that of β-purothionin, α-hordothionin displays reduced fluctuating motions. Moreover, α-hordothionin is more resistant to the presence of metal ions than β-purothionin. Mg+2 ions do not affect α-hordothionin, whereas K+ ions induce perturbations in the α2 helix, modify dynamics and electrostatic properties. Nevertheless, these changes are considerably smaller than those in β-purothionin. The proposed mechanism of metal ion-based inhibition involves the hydrogen bonding network of Arg5–Arg30–Gly27, which regulates dynamic unfolding of the α2 C-end which is similar to β-purothionin response. The key residues responsible for the increased resistance for α-hordothionin are Gly27 and Gly42 which replace Asn27 and Asp42 involved into the mechanism of metal ion-based inhibition in β-purothionin. Comparison of MD simulations of α-hordothionin with β-purothionin reveals dynamic properties which we believe are intrinsic properties of thionins with four disulphide bonds.