temporin and dodecylphosphocholine

We investigated the molecular mechanisms of short peptides interacting with membrane-mimetic systems. Three short peptides were selected for this study: penetratin as a cell-penetrating peptide (CPP), and temporin A and KSL as antimicrobial peptides (AMP). We investigated the detailed interactions of the peptides with dodecylphosphocholine (DPC) and sodium dodecyl sulfate (SDS) micelles, and the subsequent peptide insertion based on free energy calculations by using all-atomistic molecular dynamics simulations with the united atom force field and explicit solvent models. First, we found that the free energy barrier to insertion for the three peptides is dependent on the chemical composition of the micelles. Because of the favorable electrostatic interactions between the peptides and the headgroups of lipids, the insertion barrier into an SDS micelle is less than a DPC micelle. Second, the peptides' secondary structures may play a key role in their binding and insertion ability, particularly for amphiphilic peptides such as penetratin and KSL. The secondary structures with a stronger ability to bind with and insert into micelles are the ones that account for a smaller surface area of hydrophobic core, thus offering a possible criterion for peptide design with specific functionalities.

Topics: Amino Acid Sequence; Antimicrobial Cationic Peptides; Biomimetics; Biophysical Phenomena; Cell Membrane; Cell-Penetrating Peptides; Depsipeptides; Kinetics; Lipid Bilayers; Micelles; Molecular Dynamics Simulation; Phosphorylcholine; Protein Structure, Secondary; Proteins; Sodium Dodecyl Sulfate; Structure-Activity Relationship

In this work, the naturally occurring antimicrobial peptides temporin A (TA) and L (TL) are studied by spectroscopic (CD and NMR) techniques and molecular dynamics simulation. We analyzed the interactions of TA and TL with sodium dodecyl sulfate (SDS) and dodecylphosphocholine (DPC) micelles, which mimic bacterial and mammalian membranes, respectively. In SDS, the peptides prefer a location at the micelle-water interface; in DPC, they prefer a location perpendicular to the micelle surface, with the N-terminus imbedded in the hydrophobic core. TL shows higher propensity, with respect to TA, in forming alpha-helical structures in both membrane mimetic systems and the highest propensity to penetrate the micelles. Hence, we have proposed a different molecular mechanism underlying the antimicrobial and hemolytic activities of the two peptides. We also designed new analogues of TA and TL and found interesting differences in their efficacy against microbial species and human erythrocytes.

Topics: Amino Acid Sequence; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Circular Dichroism; Erythrocytes; Hemolysis; Humans; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Models, Molecular; Phosphorylcholine; Proteins; Sodium Dodecyl Sulfate; Spectrometry, Mass, Fast Atom Bombardment; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization