Structural features of helical aggregates of antibacterial peptides via simulated annealing and molecular modeling.

A 27-residue stretch of amino acids encompassing two putative 13-residue amphiphilic helical segments is an important determinant of activity in the 47-residue antibacterial peptide bovine seminalplasmin. Synthetic peptides corresponding to the 27-residue stretch (P27) SLSRYAKLANRLANPKLLETFLSKWIG as well as the 13-residue segments PKLLETFLSKWIG (SPF),exhibit antimicrobial activity. An analog of SPF where E has been replaced by K(SPFK) showed improved antimicrobial properties as compared to SPF. The peptides have the ability to bind and permeabilize membranes. We have modeled helical bundles of P27 and the two 13-residue peptides SPF and SPFK using simulated annealing via molecular dynamics. Octameric but not hexameric aggregates of P27 can form channels which would allow the passage of ions. In the case of 13-residue peptides, aggregates formed by 6 monomers can conceivably form ion conducting channels. Since the ability to form channels which would allow the passage of ions across the membranes is an important determinant of the biological activities of these peptides, knowledge of the pore forming structures should help in the design of analogs with improved activities.