Certain antimicrobial peptides (AMPs) and mitochondrial targeting peptides (mTPs) share common features such as a positive net charge, helical propensity, and the ability to interact with lipid membranes[1]. While a primary function of AMPs is to disrupt membrane integrity, many mTPs interact with the mitochondrial membranes and the translocator complex, leaving the membranes intact when proteolytically degraded by matrix-located protease(s)[2]. We present a computational approach that may help rationalize the delicate balance of these effects and other sequence-activity relationships. We implemented and applied a directed evolutionary strategy for stepwise peptide morphing of one peptide into another (MoPED, Morphing of Peptides by Evolutionary Design). For the prospective application, we chose cationic peptides as representatives of both peptide classes and converted an AMP (Protonectin, start sequence)[3] into an mTP (target or “attractor” sequence). Novel peptides were generated based on a chemical similarity index (Grantham substitution matrix).[4] The target sequence served as an attractor point for evolutionary exploration of sequence space. We synthesized and tested the individual peptides that were generated during the morphing process. The designed peptides showed systematic loss of membranolytic potential with increasing distance from the start sequence. The results of biophysical and bacterial growth experiments confirmed the applicability of MoPED to designing chemically motivated peptide derivatives. Receiver operating characteristic (ROC) analysis advocates the inducible peptide α-helicity as a semi-quantitative indicator of membranolytic antimicrobial activity.