Structural Analysis and Design of Chionodracine-Derived Peptides Using Circular Dichroism and Molecular Dynamics Simulations

Antimicrobial peptides have been identified as one of the alternatives to the extensive use of common antibiotics as they show a broad spectrum of activity against human pathogens. Among these is Chionodracine ( Cnd ), a host-defense peptide isolated from the Antarctic icefish Chionodraco hamatus ,...

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Bibliographic Details
Published in:International Journal of Molecular Sciences
Main Authors: Stefano Borocci, Giulia Della Pelle, Francesca Ceccacci, Cristina Olivieri, Francesco Buonocore, Fernando Porcelli
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2020
Subjects:
chionodracines
antimicrobial peptides
circular dichroism
molecular dynamics
peptide-membrane interaction
Biology (General)
QH301-705.5
Chemistry
QD1-999
Antarctic
The Antarctic
Antarc*
Icefish
Online Access:https://doi.org/10.3390/ijms21041401
https://doaj.org/article/bdd9760b910148608d5985774af5cc92
Description
Summary:Antimicrobial peptides have been identified as one of the alternatives to the extensive use of common antibiotics as they show a broad spectrum of activity against human pathogens. Among these is Chionodracine ( Cnd ), a host-defense peptide isolated from the Antarctic icefish Chionodraco hamatus , which belongs to the family of Piscidins. Previously, we demonstrated that Cnd and its analogs display high antimicrobial activity against ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species). Herein, we investigate the interactions with lipid membranes of Cnd and two analogs, Cnd-m3 and Cnd-m3a , showing enhanced potency. Using a combination of Circular Dichroism, fluorescence spectroscopy, and all-atom Molecular Dynamics (MD) simulations, we determined the structural basis for the different activity among these peptides. We show that all peptides are predominantly unstructured in water and fold, preferentially as α-helices, in the presence of lipid vesicles of various compositions. Through a series of MD simulations of 400 ns time scale, we show the effect of mutations on the structure and lipid interactions of Cnd and its analogs. By explaining the structural basis for the activity of these analogs, our findings provide structural templates to design minimalistic peptides for therapeutics.

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