A new antimicrobial hybrid peptide sequence has been synthesized from pediocin A (N-terminal) and plantaricin 149A (C-terminal). Previous studies of circular dichroism and fluorescence spectroscopic studies have shown a disordered to ordered conformational transition of the peptide upon binding to POPG but not to POPC. Optical microscopy measurements have indicated that at low concentrations the peptide causes the disruption of POPG membrane of vesicles and formation of small, heterogeneous complexes of phospholipids and peptides. In order to analyze action mechanism of the hybrid peptide, molecular dynamics (MD) simulations were carried out using the GROMOS parameter set 54A7 (atomistic level) and MARTINI (coarse-grain level). The peptide concentration was taken into account. The systems were analyzed with respect to time-dependent (peptide secondary structure map and lipid tilt angle), and average properties (density profiles and deuterium order parameters).Our MD simulations show that the peptide adsorbs on both PG and PC membranes via electrostatic interactions. Only upon binding to the PG surface there is an increase of helical content compared to the peptide in solution. Higher helical content is also observed for the single peptide embedded in PG compared to PC membranes which is in agreement with experimental data. The density of the membrane medium makes conformational transition of the peptide embedded slower than on the surface of the membrane. The results suggest a mechanism of membrane disruption without deep penetration of the peptide, but only from a given peptide concentration threshold. Evidence for that comes from increased disorder of the membrane and persistent interactions between the peptide and membrane headgroups throughout the membrane disruption process. Our findings suggest that the hybrid peptide disrupt the membrane via a carpet-like mechanism (in a V-shape) which has also been postulated for the action of Pediocin A and Plantaricin 149A [1,2].  [1] Gaussier et al. App. Environm. MicroBiol., 69, 6777 (2003) ; [2] Lopes et al., BBA, 1788, 2252 (2009) .

Molecular dynamics studies of a pediocin-plantaricin hybrid peptide in POPG:POPC bilayers

248th National Meeting (2014)

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