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

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• 作者：Yana Gofman ; Sebastian Linser ; Agnieszka Rzeszutek ; Dalit Shental-Bechor ; Sergio S. Funari ; Nir Ben-Tal ; Regine Willumeit
• 刊名：Journal of Physical Chemistry B
• 出版年：2010
• 出版时间：April 1, 2010
• 年：2010
• 卷：114
• 期：12
• 页码：4230-4237
• 全文大小：232K
• 年卷期：v.114,no.12(April 1, 2010)
• ISSN：1520-5207

文摘

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.