Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study

Abstract

Background: Lactoferrampin (LFampin), Lactoferricin (LFcin), and LFchimera are three well-known antimicrobial peptides derived from Lactoferrin and proposed as alternatives for antibiotics. Although the intracellular activity of these peptides has been previously demonstrated, their mode of action is not yet fully understood. Here, we performed a molecular dynamics simulation study to understand the molecular interactions between camel Lactoferrin derived peptides, including CLFampin, CLFcin, and CLFchimera, and DNA as an important intracellular target. Results: Our results indicate that all three peptides bind to DNA, albeit with different propensities, with CLFchimera showing the highest binding affinity. The secondary structures of the peptides, modeled on Lactoferrin, did not undergo significant changes during simulation, supporting their functional relevance. Main residues involved in the peptide-DNA interaction were identified based on binding free energy estimates calculated over 200 ns, which, as expected, confirmed strong electrostatic interactions between DNA phosphate groups and positively charged peptide side chains. Interaction between the different concentrations of CLFchimera and DNA revealed that after binding of four copies of CLFchimera to DNA, hydrogen bonds between the two strands of DNA start to break from one of the termini. Conclusions: Importantly, our results revealed that there is no DNA-sequence preference for peptide binding, in line with a broad antimicrobial activity. Moreover, the results showed that the strength of the interaction between DNA and CLFchimera is concentration dependent. The insight provided by these results can be used for the rational redesign of natural antimicrobial peptides targeting the bacterial DNA.

Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation

“…in vitro antibacterial, anti-biofilm and antioxidant activity of the recombinant chimeric peptide were determined on some food spoilage bacterial strains. Finally, using computational modeling approaches we try to predict peptide interaction to lipopolysaccharides (LPS) and DNA as two main targets in bacteria [15,36,50,51].…”

Impact of Hydrolyzed Camel´s Whey Protein Concentrate on Soft Cheese Quality

“…The results for all treated cheese samples were within these permissible limits until end of refrigerated storage, while the higher levels of TBC (>10 5 cfu/g) were showed in control group. A significant reduction of psychrophilic counts in all treated cheese groups may attributed to effectivness of peptides in camel whey proteins hydrolysates mainly potent camel Lactoferricin peptides as demonstrated by Pirkhezranian et al (2020).…”

Antibacterial Activity of cLFchimera and its Synergistic Potential with Antibiotics against Some Foodborne Pathogens Bacteria

“…In this regards, Reyes-Cortes et al, (2017) showed that this chimeric peptide mediated its antibacterial activity by entering the cytoplasm through translocation across the bacterial membrane and possibly interacting with internal organelles [33]. Consistent with these results, Pirkhezranian et al, (2020 a, b) using molecular simulation analysis showed that cLFchimera and its derivatives had a higher a nity for DNA interaction and hypothesized this chimeric peptide mediated its activity by intramolecular mechanisms which interference DNA related pathways such as DNA replication [34,35]. However, treatment of all bacteria with antibiotics and their combinations (antibiotics + peptide) resulted signi cantly increased the release of cellular contents.…”