Study On The Membrane-penetrating Mechanism Of Lactoferricin Transmembrane Peptide

Cell-penetrating peptides are a kind of peptides that can carry a various of active materials into the cell. It has a good application prospect in the targeted therapy for disease, enhancing drug absorption and other fields. Parts of antibacterial peptides have the characteristics of cell-penetrating peptides. Such as: N-terminal 20-25 amino acid residues bLFcin6(RRWQWR) from lactoferricin B is the antibacterial active center, and also have cell penetrating ability. These residues almost keep all the biological functions of the whole protein. However, the antibacterial and membrane-penetrating mechanism of bLFcin6 still exist many problems to be further discussed. Molecular dynamics simulations have been proven to be a valuable tool to study the peptide-membranes interaction. Hence, the molecular dynamics simulation of bLFcin6 peptide and three different cell membranes, can explain the possible antibacterial penetrating mechanism of bLFcin6 at the atomic level, and provide powerful supplement for experimental study.The aim of this paper is to explore the interaction between bLFcin6 peptide and different bilayer lipid membranes by comparing the centroid distance of peptide-membranes, the formation of hydrogen bonds number and interaction free energy. Simulation results shown that bLFcin6 peptide can entered into the carbonyl parts of DPPC membrane and interacted with the hydrophopic tail; BLFcin6 peptide interacted with hydrophilic head of POPG membrane, but not entered into the membrane; BLFcin6 peptide did not contact with POPC membrane. Furthermore, we calculated the average distance and number of hydrogen bond between different amino acid residues and the membrane formation. The results indicated that the N-terminal Argnine residues contact with the membrane firstly, and form the most hydrogen bonds with the membrane phosphate group. Arginine residues plays an important role in peptide-membranes interaction. In addition, we calculated the interaction free energy of the bLFcin6 peptide and different membranes. The results shown that the BLFcin6 peptide tend to combined with POPG membrane, followedby the DPPC membrane and combined with POPC membrane is the weakest. Finally,we analyzed the influence of bLFcin6 peptide on the structure of membrane. The results indicated that single bLFcin6 peptide has little influence on the thickness of different phospholipid membranes. We also calculated the mean square displacement(MSD) and the order parameter of hydrophobic side chains for the three different peptide-phospholipid membrane systems and pure membrane systems. For MSD, the value was increased when adding bLFcin6 peptide, and the bLFcin6 peptide has more influence on DPPC and POPG membrane. For the order parameter of hydrophobic side chains, the value was decreased when adding bLFcin6 peptide, and the bLFcin6 peptide has more influence on POPG membrane because of the strong electrostatic interaction between bLFcin6 and POPG membrane. The exist of bLFcin6 peptide make it more easy to penetrate membrane. BLFcin6 have different infiltration capacity to different membrane, which is closely related to the structure of phospholipid molecules. These studies will provide in depth mechanistic understanding for bLFcin6 peptide.