Molecular Dynamics Study about the Antibacterial Activity of Aurein 1.2 and LLAA against DPPC lipid Bilayer

Antimicrobial peptides (AMPs) are a class of amphipathic and cationic peptides that are naturally found in the innate immune system of wide variety of organisms [1]. AMPs display antibacterial activity against microbial membranes [2]. Aurein 1.2 is an antimicrobial peptide that is found in the skin secretion of an Australian frog. LLAA is a human LL-37 derived analog for Aurein 1.2 which has similarity with Aurein 1.2 in its sequence [3, 4]. In this study in order to explore the key differences between Aurein 1.2 and LLAA we performed 16 molecular dynamics simulations by using GROMACS package. In order to evaluate absorption and penetration of peptides into the membrane, simulations of a peptides placed on the surface of DPPC bilayer were performed. To investigate the mechanism of action of these peptides in lipid bilayer, simulations of individual and group of peptides inside lipid bilayer were also done. We have also performed the simulations of sample membranes without peptides and group of peptides in the water. Results of penetration simulations revealed that peptides attract to the membrane with their N terminal and penetrate into the bilayer with their C terminal. In the bilayer, it was observed that the carpet or toroidal pore mechanism of action is working in the case of our peptides. Comparison between Aurein 1.2 and LLAA shows that LLAA leads to more penetration for phospholipid head groups and have better function than Aurein 1.2. Exploring RMSF and secondary structure indicates that LLAA has more structural flexibility. Moreover, Aurein maintains its helicity content more than LLAA during simulations. These results could explain better antibacterial performance of LLAA peptide. The comparison of individual and group peptides indicated that group peptides have more perturbation effect on lipid bilayer, meaning that cooperative effect can improve antimicrobial activity.