A molecular dynamics study on the antibacterial action of the two peptideds, aurein 1.2 and LLAA

Aurein peptides constitute a large family of antimicrobial peptides that secrete from the skin of Litoria genus of Australian frogs. Aurein 1.2 is the smallest peptide from this family, with a relatively simple structure which acts against both bacterial and cancer cells. LLAA derived from a human antimicrobial peptide (LL-37) has a very similar sequence with aurein 1.2 and has been shown to have stronger antibacterial activity respect to aurein. In this research, we studied the interaction of aurein 1.2 and LLAA with a model bacterial membrane using molecular dynamics simulation. For modeling the bacterial membrane, we used POPE|POPG lipid of 3:1 ratio. The structural change of aurein 1.2 and LLAA while inserting into membrane from water environment has been presented in this research. We did our simulations using GROMACS package in atomistic scales using a hybrid forcefield between gromos53a6 and berger-lipid parameters. Four simulations have been setup for the interaction of “single aurein”, “5 aureins”, “single LLAA”, “5 LLAAs” with bacterial membrane and done for 1 microsecond. For the initial configuration, we put the peptides vertically on the surface of the membrane with peptide N-terminal regions next to the membrane surface. We observed that the structure of peptides changed while crossing from water to membrane environment. Aurein was observed to be unstructured in water and when it attached to the membrane surface, it folded into an alpha helix structure because of its amphipatic environment. This structural change has been observed previously in experimental research [1]. Results revealed that the most prominent mode of action for both LLAA and aurein is that they insert into the membrane by attaching their N-terminal into the membrane surface and inserting their C-terminal into the membrane core. Moreover, LLAA peptide illustrates a more pronounced insertion relative to the aurein.