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How the Antimicrobial Peptides Kill Bacteria: Computational Physics Insights

Published online by Cambridge University Press:  20 August 2015

Licui Chen ,
Lianghui Gao ,
Weihai Fang  and
Leonardo Golubovic
Licui Chen
Affiliation:
College of Chemistry, Beijing Normal University, Beijing 100875, China
Lianghui Gao*
Affiliation:
College of Chemistry, Beijing Normal University, Beijing 100875, China
Weihai Fang
Affiliation:
College of Chemistry, Beijing Normal University, Beijing 100875, China
Leonardo Golubovic
Affiliation:
Physics Department, West Virginia University, Morgantown, West Virginia 26506-6315, USA
*
*Corresponding author.Email:lhgao@bnu.edu.cn
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Abstract

In the present article, coarse grained Dissipative Particle Dynamics simulation with implementation of electrostatic interactions is developed in constant pressure and surface tension ensemble to elucidate how the antimicrobial peptide molecules affect bilayer cell membrane structure and kill bacteria. We find that peptides with different chemical-physical properties exhibit different membrane obstructing mechanisms. Peptide molecules can destroy vital functions of the affected bacteria by translocating across their membranes via worm-holes, or by associating with membrane lipids to form hydrophilic cores trapped inside the hydrophobic domain of the membranes. In the latter model, the affected membranes are strongly buckled, in accord with very recent experimental observations [G. E. Fantner et al., Nat. Nanotech., 5 (2010), pp. 280-285].

Keywords

87.15.-v82.70.Uv87.15.kt87.15.A-Antimicrobial peptidebilayer membranedissipative particle dynamics

Information

Type
Research Article
Information
Communications in Computational Physics , Volume 11 , Issue 3 , March 2012 , pp. 709 - 725
Copyright
Copyright © Global Science Press Limited 2012

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References

[1]Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P., Molecular Biology of Cell, Garland Science, New York, 2002.Google Scholar
[2]Denmark, T. H., Themed issue: Membrane biophysics, Soft Matt., 5 (2009), pp. 3145- 3147.Google Scholar
[3]Zasloff, M., Antimicrobial peptides of multicellular organisms, Nature (London, United Kingdom), 415 (2002), pp. 389–395.Google Scholar
[4]Brogden, K. A., Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol., 3 (2005), pp. 238–250.Google Scholar
[5]Matsuzaki, K., Why and how are peptide-lipid interactions utilized for self-defense? Maga-inins and tachyplesins as archetypes, Biochim. Biophys. Acta., 1462 (1999), pp. 1–10.CrossRefGoogle ScholarPubMed
[6]Shai, Y., Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides, Biochim. Biophys. Acta., 1462 (1999), pp. 55–70.CrossRefGoogle ScholarPubMed
[7]Yang, L., Weiss, T. M., Lehrer, R. I., and Huang, H. W., Crystalization of antimicrobial pores in membranes: Magainin and protegrin, Biophys. J., 79 (2000), pp. 2002–2009.Google Scholar
[8]La Rocca, P., Biggin, P. C., and Tieleman, D. P., Simulation studies of the interaction of antimicrobial peptides and lipid bilayers, Biochim. Biophys. Acta., 1462 (1999), pp. 185–200.Google Scholar
[9]Lin, J. H. and Baumgaertner, A., Stability of a melittin pore in a lipid bilayer: A molecular dynamics study, Biophys. J., 78 (2000), pp. 1714–1724.Google Scholar
[10]Leontiadou, H., Mark, A. E., and Marrink, S. J., Antimicrobial peptide in action, J. Am. Chem. Soc., 128 (2006), pp. 12156–12161.Google Scholar
[11]Herce, H. D. and Garcia, A. E., Molecular dynamics simulations suggest a mechanism for translocation of the HIV-1 Tat peptide across lipid membranes, Proc. Natl. Acad. Sci. U. S. A., 104 (2007), pp. 20805–20810.CrossRefGoogle ScholarPubMed
[12]Jean-Francois, F., Elezgaray, J., Berson, P., Vacher, P., and Duforc, E. J., Pore formation induced by an antimicrobial peptide: Electrostatic effects, Biophys. J., 95 (2008), pp. 5748–5756.CrossRefGoogle ScholarPubMed
[13]Lopez, C. F., Nielsen, S. O., Moore, P. B., and Klein, M. L., Understanding nature’s design for ananosyringe, Proc. Natl. Acad. Sci. U. S. A., 101 (2004), pp. 4431–4434.CrossRefGoogle Scholar
[14]Lopez, C. F., Nielsen, S. O., Moore, P. B., and Klein, M. L., Structure and dynamics of model pore insertion into a membrane, Biophys. J., 88 (2005), pp. 3083–3094.Google Scholar
[15]Lopez, C. F., Nielsen, S. O., Srinivas, G., DeGrado, W. F., and Klein, M. L., Probing membrane insertion activity of antimicrobial polymers via coarse-grain molecular dynamics, J. Chem. Theor. Comput., 2 (2006), pp. 649–655.Google Scholar
[16]Venturoli, M., Smit, B., and Sperotto, M. M., Simulation studies of protein-induced bilayer deformations, and lipid-induced protein tilting, on a mesoscopic model for lipid bilayers with embedded proteins, Biophys. J., 88 (2005), pp. 1778–1798.Google Scholar
[17]Illya, G., and Deserno, M., Coarse-grained simulation studies of peptide-induced pore formation, Biophys. J., 95 (2008), pp. 4163–4173.Google Scholar
[18]Gao, L. and Fang, W., Effects of induced tension and electrostatic interactions on the mechanisms of antimicrobial peptide translocation across lipid bilayer, Soft Matt., 5 (2009), pp. 3312–3318.CrossRefGoogle Scholar
[19]Espanol, P. and Warren, P. B., Statistical mechanics of dissipative particle dynamics, Europhys. Lett., 30 (1995), pp. 191–196.Google Scholar
[20]Groot, R. D. and Warren, P. B., Dissipative particle dynamics: Bridging the gap between atomistic and mesoscopic simulation, J. Chem. Phys., 107 (1997), pp. 4423–4435.CrossRefGoogle Scholar
[21]Groot, R. D. and Rabone, K. L., Mesoscopic simulation of cell membrane damage, morphology change and rupture by nonionic surfactants, Biophys. J., 81 (2001), pp. 725–736.Google ScholarPubMed
[22]Martyna, G. J., Tobias, D.J., and Klein, M.L., Constant pressure molecular dynamics algorithms, J. Chem. Phys., 101 (1994), pp. 4177–4189.Google Scholar
[23]Jakobsen, A. F., Constant-pressure and constant-surface tension simulations in dissipative particle dynamics, J. Chem. Phys., 122 (2005), pp. 124901.Google Scholar
[24]Groot, R. D., Electrostatic interactions in dissipative particle dynamics-simulation of poly-electrolytes and anionic surfactants, J. Chem. Phys., 118 (2003), pp. 11265–11277.Google Scholar
[25]Hunenberger, P. H., Calculation of the group-based pressure in molecular simulations. I. A general formulation including Ewald and particle-particle-particle-mesh electrostatics, J. Chem. Phys., 116 (2002), pp. 6880–6897.Google Scholar
[26]Gao, L. and Fang, W., Communications: Self-energy and corresponding virial contribution of electrostatic interactions in dissipative particle dynamics: Simulations of cationic lipid bilayers, J. Chem. Phys., 132 (2010), pp. 031102–031104.Google Scholar
[27]Fantner, G. E., Barbero, R. J., Gray, D. S. and Belcher, A. M., Kinetics of antimicrobial peptide activity measured on individual bacterial cells using high-speed atomic force microscopy, Nat. Nanotech., 5 (2010), pp. 280–285.CrossRefGoogle ScholarPubMed