Structural changes induced in thionins by chloride anions as determined by molecular dynamics simulations.

Computational analysis of two membrane-permeabilizing peptides, barley alpha-hordothionin and wheat beta-purothionin, revealed that anions can trigger dynamic and structural changes in the thionin antiparallel double alpha-helix core. Analysis of the molecular dynamics simulations demonstrated that anions induced unfolding of the alpha2 and alpha1 helices at the carboxyl ends which are located on the opposite ends of the alpha-helix core. An internalized water molecule was observed inside the unfolded alpha2 C-end. Strong interactions of anions with the R30 regulating network or simultaneous interactions of anions with the phospholipid-binding site and the R30 hydrogen bonding network triggered unfolding of the alpha2 C-end. An increase of anion density for two residues of the phospholipid-binding site (K1, R17, and Q22) or R17 and R19 and a preceding unfolding of the alpha2 C-end were necessary for unfolding of the alpha1 C-end. Anions interacted primarily with residues of the phospholipid-binding site and the R30 network while the alpha1/alpha2 hydrophobic region was void of anions. However, during strong interactions of anions with the R30 network and phospholipid-binding site, the alpha1/alpha2 hydrophobic region attracted anions which interacted with conserved residues of the alpha1 C-end. Analysis of anion-induced rearrangements pointed to auxiliary residues of the R30 network and the phospholipid-binding site. Induction of conformational changes on the opposite ends of the alpha-helix core by interactions of anions with the phospholipid-binding site may be relevant to a mechanism of membrane-permeabilizing activity.