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Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study
Mohammadhadi Sekhavati
Ferdowsi University of Mashhad
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8091-3798
License:
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View the published version at BMC Genomics.
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
Keywords
Antimicrobial peptide, DNA binding, Lactoferrin, Molecular dynamics simulation, CLFchimera
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CURRENT STATUS: Published
Version 2
Posted 31 Dec, 2019
Published
On 20 Jan, 2020
No community comments so far
Editorial decision: Accept
On 06 Jan, 2020
Review #1 received
Received 02 Jan, 2020
Reviewer #1 agreed
On 01 Jan, 2020
Reviewers invited
Invitations sent on 31 Dec, 2019
Editor assigned
On 27 Dec, 2019
Submission checks complete
On 26 Dec, 2019
Editor invited
On 26 Dec, 2019
No comments provided
Editorial decision: Major revision
On 25 Nov, 2019
Review #2 received
Received 25 Oct, 2019
Reviewer #3 agreed
On 22 Oct, 2019
Reviewer #2 agreed
On 11 Oct, 2019
Review #1 received
Received 21 Jul, 2019
Reviewers invited
Invitations sent on 11 Jul, 2019
Reviewer #1 agreed
On 11 Jul, 2019
Submission checks complete
On 19 Jun, 2019
Editor invited
On 10 Jun, 2019
Editor assigned
On 10 Jun, 2019
First submitted
On 08 Jun, 2019
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Subject Areas
Epigenetics & Genomics
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This preprint is under consideration at BMC Genomics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study
Mohammadhadi Sekhavati
Ferdowsi University of Mashhad
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8091-3798
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 31 Dec, 2019
Published
On 20 Jan, 2020
No community comments so far
Editorial decision: Accept
On 06 Jan, 2020
Review #1 received
Received 02 Jan, 2020
Reviewer #1 agreed
On 01 Jan, 2020
Reviewers invited
Invitations sent on 31 Dec, 2019
Editor assigned
On 27 Dec, 2019
Submission checks complete
On 26 Dec, 2019
Editor invited
On 26 Dec, 2019
No comments provided
Editorial decision: Major revision
On 25 Nov, 2019
Review #2 received
Received 25 Oct, 2019
Reviewer #3 agreed
On 22 Oct, 2019
Reviewer #2 agreed
On 11 Oct, 2019
Review #1 received
Received 21 Jul, 2019
Reviewers invited
Invitations sent on 11 Jul, 2019
Reviewer #1 agreed
On 11 Jul, 2019
Submission checks complete
On 19 Jun, 2019
Editor invited
On 10 Jun, 2019
Editor assigned
On 10 Jun, 2019
First submitted
On 08 Jun, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Genomics.
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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