Cell-penetrating and membrane-pore forming peptides are a class of membrane-active peptides. They are short sequence peptides having both hydrophilic and lipophilic combinations of amino acids. These peptides can have contrast functional diversity. Peptides encoded by viruses function as viroporins and play a critical role in viral replication, propagation, and pathogenesis. One such peptide is the Ebola virus delta peptide, which forms a pore in the host cell membrane. Another set of pore-forming peptides are antimicrobial Lantibiotic peptides that may be useful for killing antibiotic resistant bacteria by disrupting the bacterial membrane through two different possible mechanisms. Not only can they form pores that disrupt the bacterial membrane, Lantibiotics can also hinder the function of a bacterial membrane molecule, Lipid II, that is essential for cell wall biosynthesis.
I performed Molecular Dynamics (MD) simulation to investigate the membrane pore-forming mechanism of the Ebola virus delta peptide. I found that the Ebola virus delta peptide forms a pentameric pore in the host cell membrane. The pore is selective for negatively charged ions, and the disulfide link between Cysteine 29 and 38 is essential for stable and effective membrane-pore formation. Similarly, I studied Lipid II binding and membrane-pore forming activity of several Lantibiotics: Nisin, Mutacin 1140, Gallidermin, NAI107, and NVB302. The computational results from MD simulations show that Nisin forms the most effective water channel in the bacterial membrane, but Gallidermin has the best Lipid II binding profile. Mutacin 1140 also binds strongly with Lipid II and forms an efficient water channel in the bacterial membrane. I also performed MD computations on a variety of mutated peptides of Mutacin 1140 and the Ebola virus delta peptides and investigated their water solubility, Lipid II binding, and membrane insertion profile. These results provide insight into the possible antimicrobial peptides with an optimized drug profile.