Skip to main content
SpringerLink
Log in

Lipopolysaccharide Membrane Building and Simulation

  • Protocol
  • First Online:
Glycoinformatics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1273))

Abstract

While membrane simulations are widely employed to study the structure and dynamics of various lipid bilayers and membrane proteins in the bilayers, simulations of lipopolysaccharides (LPS) in membrane environments have been limited due to their structural complexity, difficulties in building LPS-membrane systems, and lack of the appropriate molecular force fields. In this work, as a first step to extend CHARMM-GUI Membrane Builder to incorporate LPS molecules and to explore their structures and dynamics in membrane environments using molecular dynamics simulations, we describe step-by-step procedures to build LPS bilayer systems using CHARMM and the recently developed CHARMM carbohydrate and lipid force fields. Such procedures are illustrated by building various bilayers of Escherichia coli R1.O6 LPS and the presentation of preliminary simulation results in terms of per-LPS area and density distributions of various components along the membrane normal.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Brade H, Opal SM, Vogel SN, Morrison DC (eds) (1999) Endotoxin in health and disease. Marcel Dekker, NY

    Google Scholar 

  2. Knirel YA, Valvano, MA (eds) (2011) Bacterial polysaccharides. Structure, chemical synthesis, biogenesis and interaction with host cells. Springer-Verlag, Wien

    Google Scholar 

  3. Silipo A, Castro DC, Lanzetta R, Parrilli M, Molinaro A (2010) Lipopolysaccharides. In: König H, Claus H, Varma A (eds) Prokaryotic cell wall compounds. Springer, Berlin, pp 133–153

    Chapter  Google Scholar 

  4. Wang X, Quinn PJ (2010) Endotoxins: lipopolysaccharides of gram-negative bacteria. In: Wang X, Quinn PJ (eds) Endotoxins: structure, function and recognition, subcellular biochemistry. Springer, Dordrecht, pp 3–25

    Chapter  Google Scholar 

  5. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  CAS  PubMed  Google Scholar 

  6. Stenutz R, Weintraub A, Widmalm G (2006) The structures of Escherichia coli O-polysaccharide antigens. FEMS Microbiol Rev 30:382–403

    Article  CAS  PubMed  Google Scholar 

  7. Linnerborg M, Weintraub A, Widmalm G (1999) Structural studies utilizing 13C-enrichment of the O-antigen polysaccharide from the enterotoxigenic Escherichia coli O159 cross-reacting with Shigella dysenteriae type 4. Eur J Biochem 266:246–251

    Article  CAS  PubMed  Google Scholar 

  8. Grozdanov L, Zahringer U, Blum-Oehler G, Brade L, Henne A, Knirel YA, Schombel U, Schulze J, Sonnenborn U, Gottschalk G, Hacker J, Rietschel ET, Dobrindt U (2002) A single nucleotide exchange in the wzy gene is responsible for the semirough O6 lipopolysaccharide phenotype and serum sensitivity of Escherichia coli strain Nissle 1917. J Bacteriol 184:5912–5925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Knirel YA, Widmalm G, Senchenkova SN, Jansson PE, Weintraub A (1997) Structural studies on the short-chain lipopolysaccharide of Vibrio cholerae O139 Bengal. Eur J Biochem 247:402–410

    Article  CAS  PubMed  Google Scholar 

  10. Whitfield C (2006) Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu Rev Biochem 75:39–68

    Article  CAS  PubMed  Google Scholar 

  11. Moran AP, Knirel YA, Senchenkova SN, Widmalm G, Hynes SO, Jansson PE (2002) Phenotypic variation in molecular mimicry between Helicobacter pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms—acid-induced phase variation in Lewis(X) and Lewis(Y) expression by H. Pylori lipopolysaccharides. J Biol Chem 277:5785–5795

    Article  CAS  PubMed  Google Scholar 

  12. Ash WL, Zlomislic MR, Oloo EO, Tieleman DP (2004) Computer simulations of membrane proteins. Biochim Biophys Acta 1666:158–189

    Article  CAS  PubMed  Google Scholar 

  13. Gumbart J, Wang Y, Aksimentiev A, Tajkhorshid E, Schulten K (2005) Molecular dynamics simulations of proteins in lipid bilayers. Curr Opin Struct Biol 15:423–431

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Lindahl E, Sansom MSP (2008) Membrane proteins: molecular dynamics simulations. Curr Opin Struct Biol 18:425–431

    Article  CAS  PubMed  Google Scholar 

  15. Pastor RW, MacKerell AD (2011) Development of the CHARMM force field for lipids. J Phys Chem Lett 2:1526–1532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Feller SE (2000) Molecular dynamics simulations of lipid bilayers. Curr Opin Colloid Interface Sci 5:217–223

    Article  CAS  Google Scholar 

  17. Stansfeld PJ, Sansom MSP (2011) Molecular simulation approaches to membrane proteins. Structure 19:1562–1572

    Article  CAS  PubMed  Google Scholar 

  18. Lins RD, Straatsma TP (2001) Computer simulation of the rough lipopolysaccharide membrane of Pseudomonas aeruginosa. Biophys J 81:1037–1046

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Straatsma TP, Soares TA (2009) Characterization of the outer membrane protein OprF of Pseudomonas aeruginosa in a lipopolysaccharide membrane by computer simulation. Proteins 74:475–488

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Jo S, Kim T, Im W (2007) Automated builder and database of protein/membrane complexes for molecular dynamics simulations. PLoS One 2:e880

    Article  PubMed Central  PubMed  Google Scholar 

  21. Jo S, Lim JB, Klauda JB, Im W (2009) CHARMM-GUI membrane builder for mixed bilayers and its application to yeast membranes. Biophys J 97:50–58

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Brooks BR, Brooks CL, Mackerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30:1545–1614

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Guvench O, Greene SN, Kamath G, Brady JW, Venable RM, Pastor RW, Mackerell AD Jr (2008) Additive empirical force field for hexopyranose monosaccharides. J Comput Chem 29:2543–2564

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Guvench O, Hatcher E, Venable RM, Pastor RW, MacKerell AD Jr (2009) CHARMM additive all-atom force field for glycosidic linkages between hexopyranoses. J Chem Theory Comput 5:2353–2370

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Hatcher E, Guvench O, MacKerell AD Jr (2009) CHARMM additive all-atom force field for aldopentofuranoses, methyl-aldopentofuranosides, and fructofuranose. J Phys Chem B 113:12466–12476

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Klauda JB, Venable RM, Freites JA, O'Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD Jr, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114:7830–7843

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Guvench O, Mallajosyula SS, Raman EP, Hatcher E, Vanommeslaeghe K, Foster TJ, Jamison FW 2nd, Mackerell AD Jr (2011) CHARMM additive all-atom force field for carbohydrate derivatives and its utility in polysaccharide and carbohydrate-protein modeling. J Chem Theory Comput 7:3162–3180

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Mallajosyula SS, Guvench O, Hatcher ER, Mackerell AD Jr (2012) CHARMM additive all-atom force field for phosphate and sulfate linked to carbohydrates. J Chem Theory Comput 8:759–776

    Google Scholar 

  29. Jansson PE, Lindberg B, Lönngren J, Ortega C, Svenson SB (1984) Structural studies of the Escherichia coli O-antigen 6. Carbohydr Res 131:277–283

    Article  CAS  PubMed  Google Scholar 

  30. Klauda JB, Kucerka N, Brooks BR, Pastor RW, Nagle JF (2006) Simulation-based methods for interpreting x-ray data from lipid bilayers. Biophys J 90:2796–2807

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Wu EL, Engström O, Jo S, Stuhlsatz D, Yeom MS, Klauda JB, Widmalm G (2013) Molecular dynamics simulation and NMR spectroscopy studies of E. coli lipopolysaccharide structure and dynamics. Biophys. J. 105:1444–1455

    Google Scholar 

  32. Wu EL, Fleming P, Yeom MS, Widmalm G, Klauda JB, Fleming KG, Im W (2014) E. Coli Outer Membrane and Interactions with OmpLA. Biophys. J. 106:2493–2502

    Google Scholar 

Download references

Acknowledgements

This work was supported by the University of Kansas General Research Fund allocation #2301388-003, Kansas-COBRE NIH P20 RR-17708, TeraGrid resources provided by Purdue University (NSF OCI-0503992) (to W.I.) and grants from the NIH (GM070855) (to A.D.M.), and from the Swedish Research Council and the Stockholm Center for Biomembrane Research/Swedish Foundation for Strategic Research (to G.W.).

Author information

Authors and Affiliations

  1. Department of Molecular Biosciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, KS, 66045, USA

    Sunhwan Jo, Emilia L. Wu, Danielle Stuhlsatz & Wonpil Im

  2. Department of Chemical and Biomolecular Engineering and Biophysics Program, The University of Maryland, 2113 Chemical and Nuclear Engineering, College Park, MD, 20742, USA

    Jeffery B. Klauda

  3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD, 21201, USA

    Alexander D. MacKerell Jr.

  4. Department of Organic Chemistry and Stockholm Center for Biomembrane Research, Arrhenius Laboratory, Stockholm University, 106-91, Stockholm, Sweden

    Göran Widmalm

Authors
  1. Sunhwan Jo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emilia L. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danielle Stuhlsatz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeffery B. Klauda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexander D. MacKerell Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Göran Widmalm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wonpil Im
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wonpil Im .

Editor information

Editors and Affiliations

  1. Justus-Liebig-University, Giessen, Germany

    Thomas Lütteke

  2. Biognos AB, Göteborg, Sweden

    Martin Frank

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Jo, S. et al. (2015). Lipopolysaccharide Membrane Building and Simulation. In: Lütteke, T., Frank, M. (eds) Glycoinformatics. Methods in Molecular Biology, vol 1273. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2343-4_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2343-4_24

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2342-7

  • Online ISBN: 978-1-4939-2343-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation