Journal:JBSD:37

Mechanism of action of <scene name='Journal:JBSD:37/Cv/1'>antimicrobial peptides (AMPs)</scene> is one of the most important challenges of pharmaceutical and biophysical science. Although it is generally accepted that most of known antimicrobial peptides act by membrane perturbation, a detailed description of how they interact with or insert into biomembranes and how we can optimize their selectivity to target a particular group of organisms remain incomplete. In this study, we applied molecular dynamics simulation to illustrate how lipid composition of membrane bilayer would affect how AMPs change biophysical properties of membrane. We compared interaction of <scene name='Journal:JBSD:37/Cv/3'>Piscidin-1 peptide</scene> (<span style="color:lightsteelblue;background-color:black;font-weight:bold;">hydrophilic residues are colored in light-steel-blue</span>, <span style="color:coral;background-color:black;font-weight:bold;">hydrophobic residues are in coral</span> and <font color='magenta'><b>glycines are in magenta</b></font>) with two different membrane models including POPC (1-palmitoyl-oleoyl-glycero-phosphocholine) and POPG (Palmitoyl-oleoyl-phosphatidylglycerol). Our main results are the following: (i) Piscidin-1 penetrates more deeply into the zwitterionic POPC bilayer compared to the anionic POPG membrane model. (ii) Non polar residues of Piscidin-1 have the most contacts with the POPC membrane due to its uncharged nature, while the peptide interacts with negatively charged POPG membrane via electrostatic interactions. (iii) Our results demonstrate that zwitterionic and anionic lipids do not have the same response against Piscidin-1 binding. In other words, the influence of antimicrobial peptide interaction on biophysical properties of a lipid membrane is dependent to lipid composition of that membrane. These observations would help us understand how antimicrobial peptides target and enter cell membrane and they also provide critical data for designing unnatural antimicrobial peptides.