Molecular Dynamics Simulation Studies of the Orientation and Mechanism of Action of Magainin in Water and DPPC Membrane Environments

Abstract

Abstract: Antimicrobial peptides (AMPs) function as defense mediators that can act against microbial invasion in their primary host. Magainin-2 is an antimicrobial peptide with 23 amino acids isolated from the African clawed frog Xenopus laevis. This study employed the molecular dynamics (MD) simulation technique to investigate the structural changes of magainin-2 in an explicit aqueous solution and in a dipalmitoyl¬phos¬phatidyl-choline (DPPC) membrane environment with a view to understanding the dynamics of the antimicrobial peptide, the nature of the peptide-membrane interactions and the structural changes of the peptide in both aqueous solvent and membrane during the whole processes. The GROMOS96-53A6 force field and Spc216 water model were employed for the MD simulations under isothermal-isobaric conditions with periodic boundary conditions imposed on x-, y- and z- directions. Structural changes were evaluated by measuring the Radius of Gyration (Rg), Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bonds and Bilayer Thickness. Twenty-six intramolecular hydrogen bonds were found, which confirms the stability of the protein during the simulation. The radius of gyration was computed to determine its compactness with water and DPPC. From the lower value ranges of Rg (0.9–1.16 nm), RMSD (0.3–0.47 nm) and RMSF (0.1–0.6 nm) in DPPC, the Magainin-2 tends to be relatively stable in Membrane environment than in aqueous solution at a conformational state.