Computational evaluation of modified peptides from human neutrophil peptide 1 (HNP-1)

The development of bacterial resistance toward antibiotics has been led to pay attention to the antimicrobial peptides (AMPs). The common mechanism of AMPs is disrupting the integrity of the bacterial membrane. One of the most accessible targets for alpha-defensins human neutrophil peptide-1 (HNP-1) is lipid II. In the present study, we performed homology modeling and geometrical validation of human neutrophil defensin 1. Then, the conformational and physicochemical properties of HNP-1 derived peptides 2Abz(14)S(29), 2Abz(23)S(29), and HNP1 Delta C18A, as well as their interaction with lipid II were studied computationally. The overall quality of the predicted model of full protein was -5.14, where over 90% of residues were in the most favored and allowed regions in the Ramachandran plot. Although HNP-1 and HNP1 Delta C18A were classified as unstable peptides, 2Abz(14)S(29)and 2Abz(23)S(29)were stable, based on the instability index values. Molecular docking showed similar interaction pattern of peptides and HNP-1 to lipid II. Molecular dynamic simulations revealed the overall stability of conformations, though the fluctuations of amino acids in the modified peptides were relatively higher than HNP-1. Further, the binding affinity constant (Kd) of HNP-1 and 2Abz(23)S(29)in complex with lipid II was 10 times stronger than 2Abz(14)S(29)and HNP1 Delta C18A. Overall, computational studies of conformational and interaction patterns have signified how derived peptides could have displayed relatively similar antimicrobial results compared to HNP-1 in the reported experimental studies. Chemical modifications not only have improved the physicochemical properties of derived peptides compared to HNP-1, but also they have retained the similar pattern and binding affinity of peptides. Communicated by Ramaswamy H. Sarma

Automated summary

The development of bacterial resistance to antibiotics has led to the attention of antimicrobial peptides (AMPs). This study computationally investigated the interaction between derived peptides and bacterial membrane and found that the derived peptides could exhibit similar antimicrobial effects to HNP-1. Furthermore, chemical modifications improved the physicochemical properties of the peptides and retained similar binding affinity.