BIOPHYSICAL THEORY AND MODELING |
Interaction of the antimicrobial peptide cyclo(RRWWRF)with membranes by molecular dynamics simulations
Christian Appelt 1, Frank Eisenmenger 1, Ronald Kühne 1, Peter Schmieder 1 and J. Arvid Söderhäll 1*
1 Inst. Molecular Pharmacology
* To whom correspondence should be addressed. E-mail: arvid{at}fmp-berlin.de.
Submitted on March 18, 2005
Revised on April 13, 2005
Accepted on 17 June 2005
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Abstract |
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Antimicrobial peptides have in the last years gained a lot of interest, due to their potential use as a new generation of antibiotics. It is believed that this type of relatively short, amphipathic, cationic peptides target the bacterial membrane, and destroy the chemical gradients over the membrane via formation of stable or transient pores. Here we use the NMR structure of cyclo(RRWWRF) in a series of molecular dynamics simulations in membranes at various peptide-to-lipid ratios. We observe that the NMR structure of the peptide is stable also after 100 ns simulation. At a peptide-to-lipid ratio of 2/128, the membrane is only little affected, compared to a pure DPPC lipid membrane, but at a ratio of 12/128, the water-lipid interface becomes more fuzzy, the water molecules can reach deeper into the hydrophobic core and the water penetration free energy barrier changes. Moreover, we observe that the area per lipid decreases and the deuterium order parameters increase in the presence of the peptide. We suggest that the changes in the hydrophobic core together with the changes in the head groups result in an imbalance of the membrane and thus not an efficient hydrophobic barrier in the presence of the peptides, independent of pore formation.
Key Words:
DPPC, antibacterial, peptide lipid interactions, permeabillity, tryptophane and arginine rich
