Volume 9, Issue 1 (2018)                   JMBS 2018, 9(1): 17-22 | Back to browse issues page

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Doustdar F, Aghdami R, Mehrnejad F, Chaparzadeh ‎ N. Interaction of Antimicrobial Peptide Pardaxin with DPPC ‎Bilayers by Molecular Dynamics Simulation. JMBS. 2018; 9 (1) :17-22
URL: http://biot.modares.ac.ir/article-22-12832-en.html
1- Microbiology Department, Medicine Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Biology Department, Science Faculty, Azarbaijan Shahid Madani University, Tabriz, Iran
3- Life Sciences Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, ‎Iran, Life Sciences Engineering Department, New Sciences and Technologies Faculty, University of Tehran, Up the Jalal-‎Al-Ahmad Junction, Kargar-e Shomali Street, Tehran, Iran , mehrnejad@ut.ac.ir
Abstract:   (8750 Views)
Aims: Today, due to the advent of drug resistance in cancer cells against conventional drugs, attention has been paid to the development of anti-cancer drugs with new mechanisms. Pardaxin is an amphipathic polypeptide neurotoxin.The aim of this study was to investigate the interaction of antimicrobial peptide pardaxin with DPPC (composed of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine) bilayers by molecular dynamics simulation.
Materials & Methods: In the present study, simulations for different membrane environments were designed under neutral pH conditions. At first, the Linux system was used to install the VMD 1.8.6 (Visual Molecular Dynamics) software; then, Gromacs 4.5.5 software was used to perform all the simulations. The pdb peptide structure (1XC0) was prepared from the Protein Data Bank and DPPC lipid bilayer was used for lipid-peptide simulation.
Findings: During the 500 nanoseconds of simulation, the peptide was infiltrated into the membrane. In the DPPC system, at first, the number of hydrogen bonds between the peptide and the lipid bilayer were increased and, then, remained almost constant until the end of the simulation and decreased over time with the number of hydrogen bonds between peptides and water. Pardaxin contacted with the membrane surface and entered into the membrane. In the presence of the peptide, the thickness of the membrane and the range of each lipid decreased and the membrane penetration increased.
Conclusion: The mechanism of Pardaxin is dependent on the bilayer composition, so that the pardaxin peptide contacts with DPPC lipid membrane surface and enters into it.
Full-Text [PDF 1238 kb]   (1457 Downloads)    
Article Type: Original Manuscript | Subject: Agricultural Biotechnology
Received: 2016/04/26 | Accepted: 2017/12/26 | Published: 2018/05/22

1. Sorensen OE. Antimicrobial peptides in cutaneous wound healing. In: Antimicrobial peptides: Role in ‎human health and disease. Harder J, Schröder JM. Berlin: Springer International Publishing; 2016. pp. 1-15.‎ [Link] [DOI:10.1007/978-3-319-24199-9_1]
2. Gaspar D, Veiga AS, Castanho MA. From antimicrobial to anticancer peptides. A review. Front Microbiol. ‎‎2013;4:294.‎ [Link]
3. O'Connor S, Szwej E, Nikodinovic-Runic J, O'Connor A, Byrne AT, Devocelle M, et al. The anti-cancer activity ‎of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate. Biomaterials. ‎‎2013;34(11):2710-8.‎ [Link]
4. Von Deuster CI, Knecht V. Antimicrobial selectivity based on zwitterionic lipids and underlying balance of ‎interaction. Biochimi Biophys Acta. 2012;1818(9):2192-201.‎ [Link] [DOI:10.1016/j.bbamem.2012.05.012]
5. Li Y, Xiang Q, Zhang Q, Huang Y, Su Z. Overview on the recent study of antimicrobial peptides: Origins, ‎functions, relative mechanisms and application. Peptides. 2012;37(2):207-15.‎ [] [DOI:10.1016/j.peptides.2012.07.001]
6. Chen C, Hu J, Zeng P, Pan F, Yaseen M, Xu H, et al. Molecular mechanisms of anticancer action and cell ‎selectivity of short α-helical peptides. Biomaterials. 2014;35(5):1552-61.‎ [Link]
7. Mihajlovic M, Lazaridis T. Charge distribution and imperfect amphipathicity affect pore formation by ‎antimicrobial peptides. Biochim Biophys Acta. 2012;1818(5):1274-83.‎ [Link] [DOI:10.1016/j.bbamem.2012.01.016]
8. Rahmanpour A, Ghahremanpour MM, Mehrnejad F, Moghaddam ME. Interaction of Piscidin-1 with ‎zwitterionic versus anionic membranes: A comparative molecular dynamics study. J Biomol Struct Dyn. ‎‎2013;31(12):1393-403.‎ [Link] [DOI:10.1080/07391102.2012.737295]
9. Fjell CD, Hiss JA, Hancock RE, Schneider G. Designing antimicrobial peptides: Form follows function. Nat ‎Rev Drug Discov. 2011;11(1):37-51.‎ [Link]
10. Hilchie AL, Wuerth K, Hancock RE. Immune modulation by multifaceted cationic host defense ‎‎(antimicrobial) peptides. Nat Chem Biol. 2013;9(12):761-8.‎ [Link] [DOI:10.1038/nchembio.1393]
11. Yedery RD, Jerse AE. Augmentation of cationic antimicrobial peptide production with histone deacetylase ‎inhibitors as a novel epigenetic therapy for bacterial infections. Antibiotics (Basel). 2015;4(1):44-61.‎ [Link] [DOI:10.3390/antibiotics4010044]
12. Yin LM, Edwards MA, Li J, Yip CM, Deber CM. Roles of hydrophobicity and charge distribution of cationic ‎antimicrobial peptides in peptide-membrane interactions. J Biol Chem. 2012;287(10):7738-45.‎ [Link] [DOI:10.1074/jbc.M111.303602]
13. Cox E, Michalak A, Pagentine S, Seaton P, Pokorny A. Lysylated phospholipids stabilize models of ‎bacterial lipid bilayers and protect against antimicrobial peptides. Biochim Biophys Acta. ‎‎2014;1838(9):2198-204.‎ [Link] [DOI:10.1016/j.bbamem.2014.04.018]
14. Porcelli F, Buck B, Lee DK, Hallock KJ, Ramamoorthy A, Veglia G. Structure and orientation of pardaxin ‎determined by NMR experiments in model membranes. J Biol Chem. 2004;279(44):45815-23.‎ [Link] [DOI:10.1074/jbc.M405454200]
15. Oren Z, Shai Y. A class of highly potent antibacterial peptides derived from pardaxin, a pore-forming ‎peptide isolated from Moses sole fish Pardachirus marmoratus. Eur J Biochem. 1996;237(1):303-10.‎ [Link] [DOI:10.1111/j.1432-1033.1996.0303n.x]
16. Epand RF, Ramamoorthy A, Epand RM. Membrane lipid composition and the interaction of pardaxin: The ‎role of cholesterol. Protein Pept Lett. 2006;13(1):1-5.‎ https://doi.org/10.2174/092986606774502063 [Link] [DOI:10.2174/0929866510602010001]
17. Bhunia A, Domadia PN, Torres J, Hallock KJ, Ramamoorthy A, Bhattacharjya S. NMR structure of ‎pardaxin, a pore-forming antimicrobial peptide, in lipopolysaccharide micelles mechanism of outer ‎membrane permeabilization. J Biol Chem. 2010;285(6):3883-95.‎ [Link] [DOI:10.1074/jbc.M109.065672]
18. Vad BS, Bertelsen K, Johansen CH, Pedersen JM, Skrydstrup T, Nielsen NC, et al. Pardaxin permeabilizes ‎vesicles more efficiently by pore formation than by disruption. Biophys J. 2010;98(4):576-85.‎ [Link]
19. Wu SP, Huang TC, Lin CC, Hui CF, Lin CH, Chen JY. Pardaxin, a fish antimicrobial peptide, exhibits ‎antitumor activity toward murine fibrosarcoma in vitro and in vivo. Mar Drugs. 2012;10(8):1852-72.‎ [Link]
20. Li LB, Vorobyov I, Allen TW. The role of membrane thickness in charged protein–lipid interactions. ‎Biochim Biophys Acta. 2012;1818(2):135-45.‎ [Link] [DOI:10.1016/j.bbamem.2011.10.026]
21. Scheraga HA, Khalili K, Liwo A. Protein-folding dynamics: Overview of molecular simulation techniques. ‎Annu Rev Phys Chem. 2007;58:57-83.‎ [Link] [DOI:10.1146/annurev.physchem.58.032806.104614]
22. Islami M, Mehrnejad F, Doustdar F, Alimohammadi M, Khadem-Maaref M, Mir-Derikvand M, et al. Study ‎of orientation and penetration of LAH4 into lipid bilayer membranes: pH and composition dependence. Chem ‎Biol Drug Des. 2014;84(2):242-52.‎ [Link]
23. Berendsen HJC, van der Spoel D, van Drunen R. GROMACS: A message-passing parallel molecular ‎dynamics implementation. Comput Phys Commun. 1995;91(1-3):43-56.‎ [Link] [DOI:10.1016/0010-4655(95)00042-E]
24. Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR. Molecular dynamics with coupling to ‎an external bath. J Chem phys.1984;81(8):3684-90.‎ [Link] [DOI:10.1063/1.448118]
25. Hoskin DW, Ramamoorthy A. Studies on anticancer activities of antimicrobial peptides. Biochim Biophys ‎Acta. 2008;1778(2):357-75.‎ [Link]
26. Liu X, Li Y, Li Zh, Lan X, Leung HM, Li J, et al. Mechanism of anticancer effects of antimicrobial peptides. J ‎Fiber Bioeng Inform. 2015;8(1):25-36.‎ [Link]

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