Interaction of an Antimicrobial Peptide with Membranes: Experiments and Simulations with NKCS

Yana Gofman, Sebastian Linser, Agnieszka Rzeszutek, Dalit Shental-Bechor, Sergio S. Funari, Nir Ben-Tal, Regine Willumeit

Research output: Contribution to journalArticlepeer-review

Abstract

We used Monte Carlo simulations and biophysical measurements to study the interaction of NKCS, a derivative of the antimicrobial peptide NK-2, with a l-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.

Original languageEnglish
Pages (from-to)4230-4237
Number of pages8
JournalJournal of Physical Chemistry B
Volume114
Issue number12
DOIs
StatePublished - 1 Apr 2010

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