Abstract
The antimicrobial activity of CXCL14-C17 and melittin peptides has been confirmed against a broad spectrum of gram-positive and gram-negative bacteria. However, instability and toxicity are two limiting factors for these peptides. This study was aimed to design a novel truncated hybrid peptide with high stability and low toxicity through fusion between mutant analogs of melittin and CXCL14-C17. In this study, melittin(M) and CXCL14-C17-a2(C) peptides were used as a template to design new antimicrobial peptide analogs by Cell PPD server. CAMPR3, ProtParam/ExPASy examined physicochemical properties of peptide analogs. MD simulation analysis was done to evaluate stability and interaction of peptide analogs alone and in contact with model DPPC membrane. A substitution at position 6 of melittin (Ile to Arg) and two substitutions in 11th positions (Tyr to Lys) and 17th (Asn to Arg) of CXCL14-a2 were favored to increase antimicrobial property. A truncated hybrid peptide (TM1C2) was designed to improve the net charge and toxicity. RMSD and RMSF values indicated more stability of the TM1C2 peptide alone and in contact with the DPPC membrane through the hydrophilic side. The order parameter for DPPC membrane in the presence of the hydrophilic side of peptide indicated the disordering effect of the peptide on the arrangement of acyl chains. Based on the COM distance and density profile, TM1C2 peptide displayed more penetration into the membrane through the hydrophilic side. In this study, we developed an attractive procedure for designing a hybrid peptide with higher stability and antimicrobial potential. The TM1C2 peptide with higher antimicrobial and stability has more potential for penetration into the lipid membrane based on physicochemical and MD simulation results.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Change history
12 June 2023
A Correction to this paper has been published: https://doi.org/10.1007/s11756-023-01452-0
Abbreviations
- AMP:
-
Antimicrobial peptide
- MD:
-
Molecular Dynamic
- MDR:
-
Multidrug-resistant
- D:
-
Discrimination factor
- RMSF:
-
Root-mean-square fluctuations
- RMSD:
-
Root-mean-square deviation
- DPPC:
-
Dipalmitoylphosphatidylcholine membrane
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This study was supported by the Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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S.F. designed the study and revised the manuscript; L.R. performed the data analysis and interpretation. H.Z. wrote the first draft of the manuscript. B.N. discussed the results. All authors read and approved the final manuscript.
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The study was conducted after ethical approval of the ethics committee of Tabriz University of medical science, Tabriz Iran (reference number: IR.TBZMED.VCR. REC. 1397. 388).
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Farajnia, S., Rahbarnia, L., Khajehnasiri, N. et al. Design of a hybrid peptide derived from Melittin and CXCL14 –C17: A molecular dynamics simulation study. Biologia 77, 2269–2280 (2022). https://doi.org/10.1007/s11756-022-01067-x
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DOI: https://doi.org/10.1007/s11756-022-01067-x