We have created a structure-selectivity database (AMPad) of frog-derived, helical antimicrobial peptides (AMPs), in which the selectivity was determined as a therapeutic index (TI), and then used the novel concept of sequence moments to study the lengthwise asymmetry of physicochemical peptide properties. We found that the cosine of the angle between two sequence moments obtained with different hydrophobicity scales, defined as the D-descriptor, identifies highly selective peptide antibiotics. We could then use this descriptor to predict TI changes after point mutations in known AMPs, and to aid the prediction of TI for de novo designed AMPs. In combination with an amino acid selectivity index, a motif regularity index and other statistical rules extracted from AMPad, the D-descriptor enabled construction of the AMP-Designer algorithm. A 23 residue, glycine-rich, peptide suggested by the algorithm was synthesized and the activity and selectivity tested. This peptide, adepantin 1, is less than 50% identical to any other AMP, has a potent antibacterial activity against the reference organism, E. coli, and has a significantly greater selectivity (TI > 200) than the best AMP present in the AMPad database (TI = 125).