Effect of helical kink in antimicrobial peptides on membrane pore formation

Every cell is protected by a semipermeable membrane. Peptides with the rightproperties, for example Antimicrobial peptides (AMPs), can disrupt this protective barrier byformation of leaky pores. Unfortunately, matching peptide properties with their ability toselectively form pores in bacterial membranes remains elusive. In particular, the proline/glycine kinkin helical peptides was reported to both increase and decrease antimicrobial activity. We usedcomputer simulations and fluorescence experiments to show that a kink in helices affects theformation of membrane pores by stabilizing toroidal pores but disrupting barrel-stave pores. Theposition of the proline/glycine kink in the sequence further controls the specific structure oftoroidal pore. Moreover, we demonstrate that two helical peptides can form a kink-like connectionwith similar behavior as one long helical peptide with a kink. The provided molecular-level insightcan be utilized for design and modification of pore-forming antibacterial peptides or toxins.