An in silico approach to de novo design of anti-microbial peptide from inspirited Komodo dragon's original VK6 peptide

Antimicrobial peptides (AMPs) function as the foremost barrier alongside fungi, bacteria, and viruses, thereby playing a pivotal role in innate immunity. These small peptides, ranging in size from 10 to 60 amino acid residues, are generated by various organisms. Reptiles, which are classified as ancient amniotes and have a wide range of ecological niches, are considered a valuable source of antimicrobial peptides (AMPs). In this study, we designed seven new AMPs to evaluate the impact of substituting tryptophan, phenylalanine, lysine, and arginine for enhancing antimicrobial activity using bioinformatic approaches. We assessed the relevant physicochemical traits using ProtParam and APD3 tools, and performed evaluations for possible allergenicity, antigenicity, and anti-inflammatory activity. The findings indicate that substitution of threonine, alanine, and valine amino acids in AMPs with tryptophan, phenylalanine, lysine, and arginine resulted in a noteworthy enhancement of the antimicrobial efficacy of the peptides designed, as compared to the original VK6 of Komodo dragon AMPs, accompanied by improved physicochemical properties. These findings highlight the applicability of bioinformatic tools in designing and optimising novel AMPs with increased antimicrobial activity, which could be a promising approach in combating multi-drug resistant bacteria.