Mechanism of β-purothionin antimicrobial peptide inhibition by metal ions: Molecular dynamics simulation study

Wheat β-purothionin is a highly potent antimicrobial peptide which, however, is inactivated by metal ions. The key structural properties and mechanisms of inhibition of β-purothionin were investigated for the first time using unconstrained molecular dynamics simulations in explicit water. A series of simulations were performed to determine effects of temperature and the metal ions. Analyses of the unconstrained simulations allowed the experimentally unavailable structural and dynamic details to be unambiguously examined. The global fold and the α1 helix of β-purothionin are thermally stable and not affected by metal ions. In contrast, the α2 helix unfolds with shift of temperature from 300 K and in the presence of metal ions. The network of conserved residues including Arg30 and Lys5 is sensitive to environmental changes and triggers unfolding. Loop regions display high flexibility and elevated dynamics, but are affected by metal ions. Our study provides insights into the mechanism of metal ion-based inhibition.