Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study
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. Keywords: Keywords: Camel, Antimicrobial peptide, DNA, Lactoferrin, Molecular dynamics simulation
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Posted 31 Dec, 2019
On 20 Jan, 2020
On 06 Jan, 2020
Received 02 Jan, 2020
On 01 Jan, 2020
Invitations sent on 31 Dec, 2019
On 27 Dec, 2019
On 26 Dec, 2019
On 26 Dec, 2019
On 25 Nov, 2019
Received 25 Oct, 2019
On 22 Oct, 2019
On 11 Oct, 2019
Received 21 Jul, 2019
Invitations sent on 11 Jul, 2019
On 11 Jul, 2019
On 19 Jun, 2019
On 10 Jun, 2019
On 10 Jun, 2019
On 08 Jun, 2019
Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study
Posted 31 Dec, 2019
On 20 Jan, 2020
On 06 Jan, 2020
Received 02 Jan, 2020
On 01 Jan, 2020
Invitations sent on 31 Dec, 2019
On 27 Dec, 2019
On 26 Dec, 2019
On 26 Dec, 2019
On 25 Nov, 2019
Received 25 Oct, 2019
On 22 Oct, 2019
On 11 Oct, 2019
Received 21 Jul, 2019
Invitations sent on 11 Jul, 2019
On 11 Jul, 2019
On 19 Jun, 2019
On 10 Jun, 2019
On 10 Jun, 2019
On 08 Jun, 2019
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. Keywords: Keywords: Camel, Antimicrobial peptide, DNA, Lactoferrin, Molecular dynamics simulation
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