Interaction of an antimicrobial peptide with membranes: experiments and simulations with NKCS.
We used Monte Carlo simulations and biophysical measurements to study the interaction of NKCS, a derivative of the antimicrobial peptide NK-2, with a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membrane. The simulations showed that NKCS adsorbed on the membrane surface and the dominant conformation featured two amphipathic helices connected by a hinge region. We designed two mutants in the hinge to investigate the interplay between helicity and membrane affinity. Simulations with a Leu-to-Pro substitution showed that the helicity and membrane affinity of the mutant (NKCS-[LP]) decreased. Two Ala residues were added to NKCS to produce a sequence that is compatible with a continuous amphipathic helix structure (NKCS-[AA]), and the simulations showed that the mutant adsorbed on the membrane surface with a particularly high affinity. The circular dichroism spectra of the three peptides also showed that NKCS-[LP] is the least helical and NKCS-[AA] is the most. However, the activity of the peptides, determined in terms of their antimicrobial potency and influence on the temperature of the transition of the lipid to hexagonal phase, displayed a complex behavior: NKCS-[LP] was the least potent and had the smallest influence on the transition temperature, and NKCS was the most potent and had the largest effect on the temperature.
Gofman
Yana
Y
GKSS Research Center, 21502 Geesthacht, Germany.
Linser
Sebastian
S
Rzeszutek
Agnieszka
A
Shental-Bechor
Dalit
D
Funari
Sergio S
SS
Ben-Tal
Nir
N
Willumeit
Regine
R
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry*; D002942:Circular Dichroism; D008567:Membranes, Artificial; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D012542:Scattering, Radiation; D020349:Surface Plasmon Resonance
D000890:Anti-Infective Agents; D008567:Membranes, Artificial; D010455:Peptides