Multi-drug resistance is a major issue faced by the global pharmaceutical industry. Short antimicrobial peptides such as anoplins can be used to replace antibiotics, thus mitigating this issue. Antimicrobial activity, non-toxicity, and structural stability are essential features of a therapeutic drug. Antimicrobial activity and toxicity to human erythrocytes have been previously reported for anoplin and anoplin R5K T8W. This study attempts to identify a therapeutic peptide drug scaffold between these peptides by examining their structural stability, mainly based on the hydrogen bonds (H-bond) found in their structures. The static structure of anoplin R5K T8W displayed lower H-bond distances than anoplin, thereby exhibiting enhanced structural stability. Dynamic stability studies revealed that conformers of anoplin R5K T8W exhibited lower hydrogen bond distances (HBDs), higher H-bond occupancies, and higher radial distribution function (RDF) of H-bonds in comparison with conformers of anoplin. Furthermore, conformers of anoplin R5K T8W generated using 50-ns molecular dynamics simulation displayed lower conformational free energy than anoplin, thus establishing its higher structural stability. Overall, anoplin R5K T8W can be claimed as a promising scaffold that may be used for therapeutic purposes. In conclusion, H-bonds play a major role in structural stability and may aid in identification of a therapeutic peptide scaffold. Graphical abstract.
Keywords: Anoplins; Hydrogen bonds; Molecular dynamics simulation; Radial distribution function of H-bonds; Therapeutic peptide drug scaffold.