%0 journal article
%@ 1520-6106
%A Gofman, Y., Linser, S., Rzeszutek, A., Shental-Bechor, D., Funari, S.S., Ben-Tal, N., Willumeit, R.

%D 2010
%J The Journal of Physical Chemistry  B
%N 12
%P 4230-4237 
%R doi:10.1021/jp909154y
%T Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS
%U https://doi.org/10.1021/jp909154y
12 
%X 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.