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

Abstract

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 α-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 2Abz¹⁴S²⁹, 2Abz²³S²⁹, and HNP1ΔC18A, 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 HNP1ΔC18A were classified as unstable peptides, 2Abz¹⁴S²⁹ and 2Abz²³S²⁹ 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 2Abz²³S²⁹ in complex with lipid II was 10 times stronger than 2Abz¹⁴S²⁹ and HNP1ΔC18A. 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

Keywords:

• Antimicrobial peptides (AMPs)
• human neutrophil peptide-1 (HNP-1)
• LipidII
• molecular modeling

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was funded by the Pasteur Institute of Iran; Grant ID TP-9351to Neda Moazzezy as a part of her Ph.D. studentship and Iranian National Science Foundation (INSF); Grant ID97012740 to Mana Oloomi.