Study of Anticancer Peptide Interacting with Model Membranes: Molecular Dynamics Simulation

In spite of great advances in cancer therapy, there is considerable current interest in developing anticancer agents with a new mode of action because of the development of resistance by cancer cells towards current anticancer drugs. A growing number of studies have shown that some of the cationic antimicrobial peptides (AMPs), which are toxic to bacteria but not to normal mammalian cells, exhibit a broad spectrum of cytotoxic activity against cancer cells. Pardaxin, an amphipathicpolypeptide neurotoxin composed of 33 amino acids, is an AMP that was first isolated from the Red Sea Moses sole,Pardachirus marmoratus. Molecular dynamics (MD) simulations of the Pardaxin have shown that the orientation of thepeptide’s C-terminal helix depends on membrane composition. It is located on the surface of lipid bilayers composed of 1- palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and is inserted in lipid bilayers composed of 1,2-dimyristoylphosphatidylcholine (DMPC). The former suggests a carpet mechanism for bilayer disruption whereas the latter is consistent with a barrel-stave mechanism. Overall, these results indicate that the mechanism of Pardaxin is dependent on membrane composition

کلیدواژه ها:

Antimicrobial peptide ، Anti cancer drugs ، Pardaxin ، Molecular dynamics simulation