Abstract
BackgroundLactoferrampin (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.ResultsOur 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.ConclusionsImportantly, 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.
Highlights
Lactoferrampin (LFampin), Lactoferricin (LFcin), and LFchimera are three well-known antimicrobial peptides derived from Lactoferrin and proposed as alternatives for antibiotics
We have recently reported that a camel Lactoferrin chimera (CLFchimera) resulting from the fusion of the C-terminal ends of camel Lactoferricin 17–30 (CLFcin) and camel Lactoferrampin 265–284 (CLFampin) using the side chain of lysine as linker to the second peptide, has a broad-spectrum activity against both Grampositive and Gram-negative bacteria [7,8,9]
CLFchimera was obtained from the Cterm-C-term fusion of CLFampin 265–284 and CLFcin17–30, using a lysine (Lys21) as linker [7, 8]
Summary
Lactoferrampin (LFampin), Lactoferricin (LFcin), and LFchimera are three well-known antimicrobial peptides derived from Lactoferrin and proposed as alternatives for antibiotics. 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. AMPs have evolved as a natural defense mechanism for fighting microbial infections [1]. They are a diverse group of innate immune system molecules that exist in all organisms [1]. We have recently reported that a camel Lactoferrin chimera (CLFchimera) resulting from the fusion of the C-terminal ends of camel Lactoferricin 17–30 (CLFcin) and camel Lactoferrampin 265–284 (CLFampin) using the side chain of lysine as linker to the second peptide, has a broad-spectrum activity against both Grampositive and Gram-negative bacteria [7,8,9].
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