Molecular Dynamics Simulation of the Adsorption of Mung Bean Defensin VrD1 to a Phospholipid Bilayer

Defensins are small peptides with anti-microbial properties and potential use as anti-fungal agents in foods. Molecular dynamics simulation elucidated the mechanisms of anti-fungal activity, by following the interaction between mung bean defensin VrD1 peptide and a diphosphatidylcholine (DPPC) bilayer. VrD1 interacts with the bilayer, initially, via electrostatic interaction between cationic amino acid side chains of lysine and arginine and the negatively charged DPPC head group. This initial docking of the VrD1 with the interface is independent of the peptide orientation at first approach, and is similar to the mechanism observed for lysozyme, also a cationic protein. Gradual penetration of the VrD1 peptide into the acyl chain leaflet of the bilayer follows. Some change to the tertiary fold of the protein occurs upon insertion of the peptide into the bilayer, but no significant changes to the secondary structure, with evidence of a stabilization of the VrD1 conformation upon adsorption. The net effect of VrD1 penetration into the bilayer is a disruption of the acyl chain order in the DPPC, which in a cell membrane would lead to disruption of metabolic processes and ultimately to cell death.