Parallel molecular dynamics simulations of antimicrobial peptides

Molecular dynamics (MD) simulations of the wheat antimicrobial peptide â-purothionin were carried out in explicit water (~14,000 atoms) using an all-atom model. The structural properties of the peptide as a function of MD simulation, temperature, and presence of the mono- and divalent metal ions were investigated. The accuracy and scalability tests of the code Peach 3.8 for our system were performed on the Intel Xeon-based Linux cluster SuperHelix at Louisiana State University (LSU). The code showed the reliable accuracy and the parallel efficiency of 0.61 for ~14,000 particles on 16 processors. The microcanonical (MC) MD simulation of â-purothionin in water showed that all secondary structures were stable and exhibited normal conformation at 300 K initial temperature. Helicity of the peptide was found to depend strongly on temperature, consistent with experimental data. Analysis of the MD trajectories elucidated new details of temperature effects on purothionin. Thus, the á-helix á1 displayed unusual temperature resistance. The â-sheets and all four disulphide bonds were not affected by change in the range of temperature from 0 to 400 K. The residues Tyr13 and Arg30 thought to be involved in antimicrobial activity of purothionin displayed increased stability. Decrease in flexibility of the peptide largely decreased upon interaction with K+ and Mg 2+ ions. The MD simulations indicated that Mg2+ ions impaired the á-helix á2 and both ions interacted with Tyr13 and Agr30, suggesting the mechanism of cation inhibition for antimicrobial activity of purothionin. Therefore, the results reported here showed that the MC MD simulations reproduced effects of temperature and metal ions on structure of purothionin. Moreover, this study provided new insights into structural properties, and effects of temperature and metal ions on structure stability and conformation of the purothionin molecule

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

Computational analysis of two membrane-permeabilizing peptides, barley α-hordothionin and wheat β-purothionin, revealed that anions can trigger dynamic and structural changes in the thionin antiparallel double α-helix core. Analysis of the molecular dynamics simulations demonstrated that anions induced unfolding of the α2 and α1 helices at the carboxyl ends which are located on the opposite ends of the α-helix core. An internalized water molecule was observed inside the unfolded α2 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 α2 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 α2 C-end were necessary for unfolding of the α1 C-end. Anions interacted primarily with residues of the phospholipid-binding site and the R30 network while the α1/α2 hydrophobic region was void of anions. However, during strong interactions of anions with the R30 network and phospholipid-binding site, the α1/α2 hydrophobic region attracted anions which interacted with conserved residues of the α1 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 α-helix core by interactions of anions with the phospholipid-binding site may be relevant to a mechanism of membrane-permeabilizing activity. © 2009