How amphiphilic attributes of cationic dodecapeptides affect their bioactivity against gram-negative pathogens

Despite ongoing efforts, the de novo design of antibacterial peptides remains largely empirical, as there are no clear clue suggesting which amino acids play a more critical role in determining overall bioactivity. Given the complex interplay between the structural and physicochemical factors, predicting the activity based solely on the sequence is not yet achievable with current knowledge. In this study, we collected a total of 38 synthesized dodecapeptides, each comprising 12 amino acids, to investigate how their amphiphilic attributes affect their bioactivity against Gram-negative pathogens. The three key parameters including grand average of hydropathicity (GRAVY), Boman index (BI), solvent-accessible surface area (SASA) of designed peptides were analysed alongside their corresponding minimum inhibitory concentration (MIC) values. A dataset-specific observation-based range of three key parameters (GRAVY: -0.04 - 1.54; BI: -1.45 - 0.79; SASA: 1417.39 Ų - 1522.94 Ų) were identified to have higher likelihood of being effective antibacterial peptides. These explorative results offer valuable insights that may inform and guide future antibacterial peptide design.