Designing AMPs for specific tasks rather than general antimicrobial activity is another promising direction. trained support vector machines (SVMs) to predict the ability of linear and cyclic peptides to induce negative Gaussian curvature (NGC) in membranes, a critical step for membrane disruption . Differentiating between AMPs and Cell Penetrating Peptides (CPPs) often relies on pore size, with AMPs forming larger pores and CPPs smaller ones . However, computationally distinguishing these classes is challenging due to overlapping features like hydrophobicity and cationicity. Many peptides exhibit dual functionality, with CPPs displaying membrane-disrupting activity at higher concentrations . The SVM model by effectively captured the lower hydrophobicity characteristic of CPPs compared to AMPs. Higher hydrophobicity in AMPs likely extends their membrane residence time, enabling the formation of stable, larger pores. In contrast, CPPs have shorter membrane residence times and smaller pore sizes . Notably, CPPs often feature multiple arginine residues, which are more effective at inducing membrane translocation compared to shorter cationic side chains such as lysine, ornithine , frequently found in AMPs. utilized a "needle in a haystack" strategy, employing Hidden Markov Models (HMMs) and cheminformatic techniques based on inductive QSAR descriptors to predict AMP sequences from unidentified proteins. This approach achieved a remarkably high hit rate in identifying active AMP sequences. Notably, the choice of input conformation -4.2 Hit-to-lead phase: Enhancing AMPs selectivity whether non-minimized, gas-phase minimized, or minimized in a Born implicit solvent -did not significantly impact model accuracy or sensitivity . This suggests that complex conformational effects are negligible for short, unstructured peptides. The virtual peptide library generated using this cheminformatic approach exhibited high frequencies of tryptophan, arginine, and lysine . Tryptophan, in particular, was enhanced in the most active quartile, underscoring its critical role in promoting membrane insertion. In contrast, physicochemical properties such as charge, hydrophobicity, and amphipathicity were similar across all quartiles, from the most to the least active peptides. This indicates that the relative positioning of amino acids within the sequence is a key determinant of antimicrobial activity .