Tools for designing amphipathic helical antimicrobial peptides

Methods are described for the design of amphipathic helical AMPs, to improve potency and/or increase selectivity with respect to host cells. One method is based on the statistical analysis of known helical AMPs to derive a sequence template and ranges of charge, hydrophobicity, and amphipathicity (hydrophobic moment) values that lead to broad-spectrum activity, but leaves optimization for selectivity to subsequent rounds of SAR determinations. A second method uses a small database of anuran AMPs with known potency (MIC values vs. E. coli) and selectivity (HC50 values vs. human erythrocytes), as well as the concept of longitudinal moment, to suggest sequences or sequence variations that can improve selectivity. These methods can assist in the initial design of novel AMPs with useful properties in vitro, but further development requires knowledge-based decisions and a sound prior understanding of how structural and physical attributes of this class of peptides affect their mechanism of action against bacteria and host cells.