Skip to main content

Short Linear Cationic Antimicrobial Peptides: Screening, Optimizing, and Prediction

  • Protocol

Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 494))

Summary

The problem of pathogenic antibiotic-resistant bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa is worsening, demonstrating the urgent need for new therapeutics that are effective against multidrug-resistant bacteria. One potential class of substances is cationic antimicrobial peptides. More than 1000 natural occurring peptides have been described so far. These peptides are short (less than 50 amino acids long), cationic, amphiphilic, demonstrate different three-dimensional structures, and appear to have different modes of action. A new screening assay was developed to characterize and optimize short antimicrobial peptides. This assay is based on peptides synthesized on cellulose, combined with a bacterium, where a luminescence gene cassette was introduced. With help of this method tens of thousands of peptides can be screened per year. Information gained by this high-throughput screening can be used in quantitative structure-activity relationships (QSAR) analysis. QSAR analysis attempts to correlate chemical structure to measurement of biological activity using statistical methods. QSAR modeling of antimicrobial peptides to date has been based on predicting differences between peptides that are highly similar. The studies have largely addressed differences in lactoferricin and protegrin derivatives or similar de novo peptides. The mathematical models used to relate the QSAR descriptors to biological activity have been linear models such as principle component analysis or multivariate linear regression. However, with the development of high-throughput peptide synthesis and an antibacterial activity assay, the numbers of peptides and sequence diversity able to be studied have increased dramatically. Also, “inductive” QSAR descriptors have been recently developed to accurately distinguish active from inactive drug-like activity in small compounds. “Inductive” QSAR in combination with more complex mathematical modeling algorithms such as artificial neural networks (ANNs) may yield powerful new methods for in silico identification of novel antimicrobial peptides.

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

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
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

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Hancock, R.E.W. and Lehrer, R. (1998) Cationic peptides: a new source of antibiotics. Trends Biotechnol. 16, 82–88.

    Article  CAS  PubMed  Google Scholar 

  2. Finking, R. and Marahiel, M.A. (2004) Biosynthesis of nonribosomal peptides. Annu. Rev. Microbiol. 58, 453–488.

    Article  CAS  PubMed  Google Scholar 

  3. Garcia-Olmedo, F., Molina, A., Alamillo J.M., and Rodriguez-Palenzuela P. (1998) Plant defense peptides. Biopolymers 47, 479–491.

    Article  CAS  PubMed  Google Scholar 

  4. Kawabata, S., Beisel, H.G., Huber, R., et al. (2001) Role of tachylectins in host defense of the Japanese horseshoe crab Tachypleus tridentatus. Adv. Exp. Med. Biol. 484, 195–202.

    CAS  PubMed  Google Scholar 

  5. Bulet, P., Stocklin, R. and Menin, L. (2004) Anti-microbial peptides: from invertebrates to vertebrates. Immunol. Rev. 198, 169–184.

    Article  CAS  PubMed  Google Scholar 

  6. Iwanaga, S. and Kawabata, S. (1998) Evolution and phylogeny of defense molecules associated with innate immunity in horseshoe crab. Front. Biosci. 3 D973–D984.

    CAS  PubMed  Google Scholar 

  7. Imler, J.L. and Bulet, P. (2005) Antimicrobial peptides in Drosophila: structures, activities and gene regulation. Chem. Immunol. Allergy 86, 1–21.

    Article  CAS  PubMed  Google Scholar 

  8. Cannon, J.P., Haire, R.N. and Litman G.W. (2002) Identification of diversified genes that contain immunoglobulin-like variable regions in a protochordate. Nat. Immunol. 3, 1200–1207.

    Article  CAS  PubMed  Google Scholar 

  9. Litman, G.W., Anderson, M.K. and Rast, J.P. (1999) Evolution of antigen binding receptors. Annu. Rev. Immunol. 17, 109–147.

    Article  CAS  PubMed  Google Scholar 

  10. Nochi, T. and Kiyono, H. (2006) Innate immunity in the mucosal immune system. Curr. Pharm. Des. 12, 4203–4213.

    Article  CAS  PubMed  Google Scholar 

  11. Yang, D., Biragyn, A., Hoover, D.M., Lubkowski, J. and Oppenheim, J.J. (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu. Rev. Immunol. 22, 181–215.

    Article  PubMed  Google Scholar 

  12. Li, J., Xu, X., Xu, C., et al. (2007) Anti-infection peptidomics of amphibian skin. Mol. Cell. Proteomics. Epub ahead of print, Jan 31, 2007.

    Google Scholar 

  13. Yang, D., Biragyn, A., Kwak, L.W. and Oppenheim, J.J. (2002) Mammalian defensins in immunity: more than just microbicidal. Trends Immunol. 23, 291–296.

    Article  CAS  PubMed  Google Scholar 

  14. Jenssen, H., Hamill, P. and Hancock, R.E.W. (2006) Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491–511.

    Article  CAS  PubMed  Google Scholar 

  15. Papo, N. and Shai, Y. (2005) Host defense peptides as new weapons in cancer treatment. Cell. Mol. Life Sci. 62, 784–790.

    Article  CAS  PubMed  Google Scholar 

  16. Gallo, R.L., Ono, M., Povsic, T., et al. (1994) Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc. Natl. Acad. Sci. USA 91, 11035–11039.

    Article  CAS  PubMed  Google Scholar 

  17. Hancock, R.E.W. and Rozek, A. (2002) Role of membranes in the activities of antimicrobial cationic peptides. FEMS Microbiol. Lett. 206, 143–149.

    Article  CAS  PubMed  Google Scholar 

  18. Mani, R., Cady, S.D., Tang, M., Waring, A.J., Lehrer, R.I. and Hong, M. (2006) Membrane-dependent oligomeric structure and pore formation of a beta-hairpin antimicrobial peptide in lipid bilayers from solid-state NMR. Proc. Natl. Acad. Sci. USA 103, 16242–16247.

    Article  CAS  PubMed  Google Scholar 

  19. Hwang, P.M. and Vogel, H.J. (1998) Structure-function relationships of antimicrobial peptides. Biochem. Cell. Biol. 76, 235–246.

    Article  CAS  PubMed  Google Scholar 

  20. Gazit, E., Miller, I.R., Biggin, P.C., Sansom, M.S.P., and Shai, Y. (1996) Structure and orientation of the mammalian antibacterial peptide cecropin P1 within phospholipid membranes. J. Mol. Biol. 258, 860–870.

    Article  CAS  PubMed  Google Scholar 

  21. Brogden, K.A. (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol. 3, 238–250.

    Google Scholar 

  22. Paschke, M. (2006) Phage display systems and their applications. Appl. Microbiol. Biotechnol. 70, 2–11.

    Article  CAS  PubMed  Google Scholar 

  23. Westerlund-Wikstrom, B. (2000) Peptide display on bacterial flagella: principles and applications. Int. J. Med. Microbiol. 290, 223–230.

    CAS  PubMed  Google Scholar 

  24. Yan, X. and Xu, Z. (2006) Ribosome-display technology: applications for directed evolution of functional proteins. Drug Discov. Today 11, 911–916.

    Article  CAS  PubMed  Google Scholar 

  25. Pini, A., Giuliani, A., Falciani, C., et al. (2005) Antimicrobial activity of novel dendrimeric peptides obtained by phage display selection and rational modification. Antimicrob. Agents Chemother. 49, 2665–2672.

    Article  CAS  PubMed  Google Scholar 

  26. Xie, Q., Matsunaga, S., Wen, Z., et al. (2006) In vitro system for high-throughput screening of random peptide libraries for antimicrobial peptides that recognize bacterial membranes. J. Pept. Sci. 12, 643–652.

    Article  CAS  PubMed  Google Scholar 

  27. Houghten, R.A. (1985) General method for the rapid solid-phase synthesis of large numbers of peptides: Specificity of antigen-antibody interaction at the level of individual amino acids. Proc. Natl. Acad. Sci. USA 82, 5131–5135.

    Article  CAS  PubMed  Google Scholar 

  28. Pellois, J.P., Zhou, X., Srivannavit, O., Zhou, T., Gulari, E. and Gao, X. (2002) Individually addressable parallel peptide synthesis on microchips. Nat. Biotechnol. 20, 922–926.

    Article  CAS  PubMed  Google Scholar 

  29. Geysen, H.M., Meloen, R.H. and Barteling, S.J. (1984) Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc. Natl. Acad. Sci. USA 81, 3998–4002.

    Article  CAS  PubMed  Google Scholar 

  30. Frank, R. (1992) Spot synthesis: an easy technique for positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron 48, 9217–9232.

    Article  CAS  Google Scholar 

  31. Hilpert, K. and Hancock, R.E.W. (2007) Use of luminescent bacteria for rapid screening and characterization of short cationic antimicrobial peptides synthesized on cellulose by peptide array technology. Nature Protocols, 3, 1652–1660.

    Article  Google Scholar 

  32. Kamradt, T. and Volkmer-Engert, R. (2004) Cross-reactivity of T lymphocyctes in infection and autoimmunity. Mol. Divers. 8, 271–280.

    Article  CAS  PubMed  Google Scholar 

  33. Hilpert, K., Winkler, F.H.D. and Hancock, R.E.W. (2007) Peptide arrays on cellulose support: SPOT synthesis - a time and cost efficient method for synthesis of large numbers of peptides in a parallel and addressable fashion. Nature Protocols, 2,1333–1349.

    Article  CAS  PubMed  Google Scholar 

  34. Lewenza, S., Falsafi, R.K., Winsor, G., et al. (2005) Construction of a mini-Tn5-luxCDABE mutant library in Pseudomonas aeruginosa PAO1: a tool for identifying differentially regulated genes. Genome Res. 15, 583–589.

    Article  CAS  PubMed  Google Scholar 

  35. Hilpert, K., Volkmer-Engert, R., Walter, T. and Hancock, R.E.W. (2005) High-throughput generation of small antibacterial peptides with improved activity. Nat. Biotechnol. 23, 1008–1012.

    Article  CAS  PubMed  Google Scholar 

  36. Hilpert, K., Elliott, M.R., Volkmer-Engert, R., et al. (2006) Sequence requirements and an optimization strategy for short antimicrobial peptides. Chem. Biol. 13,1101–1107.

    Article  CAS  PubMed  Google Scholar 

  37. Gennaro, R., Skerlavaj, B., and Romeo, D. (1989) Purification, composition and activity of two bactenecins, antibacterial peptides of bovine neutrophils. Infect. Immun. 57, 3142–3146.

    CAS  PubMed  Google Scholar 

  38. Scocchi, M., Romeo, D., and Zanetti, M. (1994) Molecular cloning of Bac7, a praline- and arginine-rich antimicrobial peptide from bovine neutrophils. FEBS Lett. 352, 197–200.

    Google Scholar 

  39. Wu, M. and Hancock, R.E.W. (1999) Improved derivatives of bactenecin, a cyclic dodecameric antimicrobial cationic peptide. Antimicrob. Agents Chemother. 43, 1274–1276.

    CAS  PubMed  Google Scholar 

  40. Moore, A.J., Beazley, W.D., Bibby, M.C. and Devine, D.A. (1996) Antimicrobial activity of cecropins. J Antimicrob. Chemother. 37, 1077–1089.

    Article  CAS  PubMed  Google Scholar 

  41. Sipos, D., Andersson, M., and Ehrenberk, A. (1992) The structure of the mammalian antibacterial peptides cecropin P1 in solution, determined by proton-NMR. Eur. J. Biochem. 209, 163–169.

    Article  CAS  PubMed  Google Scholar 

  42. Turner, J., Cho, Y., Dinh, N.N., Waring, A.J., and Lehrer, R.I. (1998) Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils. Antimicrob. Agents Chemother. 42, 2206–2214.

    CAS  PubMed  Google Scholar 

  43. Zimmermann, G.R., Legault, P., Selsted, M.E. and Pardi, A. (1995) Solution structure of bovine neutrophil beta-defensin-12: the peptide fold of the beta-defensins is identical to that of the classical defensins. Biochemistry 34, 13663–13671.

    Article  CAS  PubMed  Google Scholar 

  44. Mandal, M., Jagannadham, M.V. and Nagaraj, R. (2001) Antibacterial activities and conformations of bovine β-defensin BNBD-12 and analogs: structural and disulfide bridge requirements for activity. Peptides 23, 413–418.

    Article  Google Scholar 

  45. Lee, D.L., and Hodges, R.S. (2003) Structure-activity relationships of de novo designed cyclic antimicrobial peptides based on Gramicidin S. Biopolymers 71,28–48.

    Article  CAS  PubMed  Google Scholar 

  46. Wadhwani, P., Afonin, S., Ieronima, M., Buerck, J., and Ulrich, A.S. (2006) Optimizad protocol for síntesis of cyclic Gramicidin S: starting amino acid is key to high yield. J. Org. Chem . 71, 55–61.

    Article  CAS  PubMed  Google Scholar 

  47. Ryge, T.S., Doisy, X., Ifrah, D., Olsen, J.E., and Hansen, P.R. (2004) New indolicidin analogues with potent antibacterial activity. J. Pept. Res. 64, 171–185.

    Article  CAS  PubMed  Google Scholar 

  48. Selsted, M.E., Tang, Y.-Q., Morris, W.L., et al. (1993) Purification, primary structures, and antibacterial activities of b-defensins, a new family of antimicrobial peptides from bovine neutrophils. J. Biol. Chem. 268, 6641–6648.

    Google Scholar 

  49. Samuelsen ,O., Haukland, H.H., Ulvatne, H. and Vorland, L.H. (2004) Anti-complement effects of lactoferrin-derived peptides. FEMS Immunol. Med. Microbiol. 41, 141–148.

    Article  CAS  PubMed  Google Scholar 

  50. Chen, H.-L., Yen, C.-C., Lu, C.-Y., Yu, C.-H., and Chen, C.-M. (2006) Synthetic porcine lactoferricin with a 20 residue peptide exhibits antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. J. Agric. Food Chem. 54, 3277–3282.

    Article  CAS  PubMed  Google Scholar 

  51. Dorschner, R.A., Pestonjamasp, V.K., Tamakuwala, S., et al. (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A streptococcus. J. Invest. Dermatol. 117, 91–97.

    Article  CAS  PubMed  Google Scholar 

  52. Gudmundsson, G.M., Lidholm, D.-A., Åsling, B., Gan, R., and Boman, H.G. (1991) The cecropin locus. Cloning and expression of a gene cluster encoding three antibacterial peptides in Hyalaphora cecropia. J. Biol. Chem. 266, 11510–11517.

    CAS  PubMed  Google Scholar 

  53. Gesell, J., Zasloff, M. and Opella, S.J. (1997) Two-dimensional 1H NMR experiments show that the 23-residue magainin antibiotic peptide is an alpha-helix in dodecylphosphocholine micelles, sodium dodecylsulfate micelles, and trifluoroethanol/water solution. J. Biomol. NMR 9, 127–135.

    Article  CAS  PubMed  Google Scholar 

  54. Wei, G., Campagna, A.N. and Bobek, L.A. (2006) Effects of MUC7 peptides on the growth of bacteria and on Streptococcus mutans biofilm. J. Antimicrob. Chemother. 57, 1100–1109.

    Article  CAS  PubMed  Google Scholar 

  55. Giacometti, A., Cirioni, O., Barchiesi, F., Del Prete, M.S. and Scalise G. (1999). Antimicrobial activity of polycationic peptides. Peptide 20, 1265–1273.

    Article  CAS  Google Scholar 

  56. Giacometti, A., Cirioni, O., Barchiesi, F., Fortuna, M., and Scalise, G. (1999) In-vitro activity of cationic peptides alone and in combination with clinically used antimicrobial agents against Pseudomonas aeruginosa. J. Antimicrob. Chemother. 44, 641–645.

    Article  CAS  PubMed  Google Scholar 

  57. Olasupo, N.A., Fitzgerald, D.J., Gasson, M.J., and Narbad, A. (2003) Activity of natural antimicrobial compounds against Escherichia coli and Salmonella enterica serovar Typhimurium. Lett. Appl. Microbiol. 36, 448–451.

    Article  Google Scholar 

  58. van den Hooven, H.W., Doeland, C.C.M., van de Kamp, M., Konings, R.N.H., Hilbers, C.W., and van de Ven, F.J.M. (1996) Three-dimensional structure of the lantibiotic nisin in the presence of membrane-mimetic micelles of dodecylphosphocholine and of dodecylsulphate. Eur. J. Biochem. 235, 382–393.

    Article  Google Scholar 

  59. Clausell, A., Rabanal, F., Garcia-Subirats, M., Alsina, M.A., and Cajal, Y. (2005) Synthesis and membrane action of polymyxin B analogues. Luminescence. 20,117–123.

    Google Scholar 

  60. Li, C., Lewis, M.R., Gilbert, A.B., et al. (1999) Antimicrobial activities of amine- and guanidine- functionalized cholic acid derivatives. Antimicrob. Agents Chemother. 43, 1347–1349.

    CAS  PubMed  Google Scholar 

  61. Regna, P.P., Solomons, I.A., Forscher, B.K., and Timreck, A.E. (1949) Chemical studies on polymyxin B. J. Clin. Invest. 28, 1022–1027.

    Article  Google Scholar 

  62. Agerberth, B., Lee, J.Y., Bergman, T., et al. (1991) Amino acid sequence of PR-39, isolation from pig intestine of a new member of the family of Pro, Arg, rich antibacterial peptides. Eur. J. Biochem. 202, 849–854.

    Article  CAS  PubMed  Google Scholar 

  63. Shi, J., Ross, C.R., Chengappa, M.M., Sylte, M.J., McVey, D.S., and Blecha, F. (1996) Antibacterial activity of a synthetic peptide (PR-26) derived from PR-39, a praline-arginine-rich neutrophil antimicrobial peptide. Antimicrob. Agents Chemother. 40, 115–121.

    CAS  PubMed  Google Scholar 

  64. Aumelas, A., Mangoni, M., Roumestand, C., et al. (1996) Synthesis and solution structure of the antimicrobial peptide protegrin-1. Eur. J. Biochem. 237, 575–583.

    Article  CAS  PubMed  Google Scholar 

  65. Fahrner, R.L, Dieckmann, T., Harwig, S.S.L., Lehrer, R.I., Eisenberg, D., and Feigon, J. (1996) Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes. Chem. Biol. (London) 3, 543–550.

    CAS  Google Scholar 

  66. Steinberg, D.A., Hurst, M.A., Jufii, C.A., et al. (1997) Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob. Agents Chemother. 41, 1738–1742.

    CAS  PubMed  Google Scholar 

  67. Kawano, K., Yoneya, T., Miyata, T., et al. (1990) Antimicrobial peptide, tachyplesin I, isolated from hemocytes of the horseshoe crab (Tachypleus tridentatus). J. Biol. Chem. 265, 15365–15367.

    CAS  PubMed  Google Scholar 

  68. Nakamura, T., Furunaka, H., Miyata, T., Tokunaga, F., Muta, T., and Iwanaga, S. (1988) Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horshoe crab (Tachypleus tridentatus). J. Biol. Chem. 263, 16709–16713.

    CAS  PubMed  Google Scholar 

  69. Perkins, R., Fang, H., Tong, W., and Welsh, W.J. (2003) Quantitative structure-activity relationship methods: perspectives on drug discovery and toxicology. Environ. Toxicol. Chem. 22, 1666–1679.

    Article  CAS  PubMed  Google Scholar 

  70. Weaver, D.C. (2004). Applying data mining techniques to library design, lead generation and lead optimization. Curr. Opin. Chem. Biol. 8, 264–270.

    Article  CAS  PubMed  Google Scholar 

  71. Lejon, T., Strom, M.B., and Svendsen, J.S. (2001) Antibiotic activity of pentadecapeptides modelled from amino acid descriptors. J. Pept. Sci. 7, 74–81.

    Article  CAS  PubMed  Google Scholar 

  72. Lejon, T., Stiberg, T., Strom, M.B., and Svendsen, J.S. (2004) Prediction of antibiotic activity and synthesis of new pentadecapeptides based on lactoferricins. J. Pept. Sci. 10, 329–335.

    Article  CAS  PubMed  Google Scholar 

  73. Strom, M.B., Stensen, W., Svendsen, J.S., and Rekdal, O. (2001) Increased antibacterial activity of 15-residue murine lactoferricin derivatives. J. Pept. Res. 57,127–139.

    Article  CAS  PubMed  Google Scholar 

  74. Jenssen, H., Gutteberg, T.J., and Lejon, T. (2005) Modeling of anti-HSV activity of lactoferricin analogues using amino acid descriptors. J. Pept. Sci. 11, 97–103.

    Article  CAS  PubMed  Google Scholar 

  75. Hellberg, S., Sjostrom, M., Skagerberg, B., and Wold, S. (1987) Peptide quantitative structure-activity relationships, a multivariate approach. J. Med.Chem. 301126–1135.

    Article  CAS  PubMed  Google Scholar 

  76. Frecer, V., Ho, B., and Ding, J.L. (2004) De novo design of potent antimicrobial peptides. Antimicrob. Agents Chemother. 48, 3349–3357.

    Article  CAS  PubMed  Google Scholar 

  77. Frece, V. (2006) QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1. Bioorgan. Medic. Chem. 14, 6065–6074.

    Article  Google Scholar 

  78. Ostberg, N., and Kaznessis, Y. (2004) Protegrin structure–activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity. Peptides 26, 197–206.

    Article  Google Scholar 

  79. Cherkasov, A. (2005) Inductive QSAR descriptors. Distinguishing compounds with antibacterial activity by artificial neural networks. Int. J. Mol. Sci. 6, 63–86.

    Article  CAS  Google Scholar 

  80. Cherkasov, A. (2005) ‘Inductive’ descriptors. 10 successful years in QSAR. Curr. Computer-Aided Drug Design 1, 21–42.

    Article  CAS  Google Scholar 

  81. Cherkasov, A. (2003) Inductive electronegativity scale. Iterative calculation of inductive partial charges. J. Chem. Inf. Comp. Sci. 43, 2039–2047.

    CAS  Google Scholar 

  82. Cherkasov, A., Shi, Z., Fallahi, M., and Hammond, G.L. (2005) Successful in silico discovery of novel non-steroidal ligands for human sex hormone binding globulin. J. Med. Chem. 48, 3203–3213.

    Article  CAS  PubMed  Google Scholar 

  83. Karakoc, E., Sahinalp, S.C., and Cherkasov, A. (2006) Comparative QSAR- and fragments distribution analysis of drugs, druglikes, metabolic substances, and antimicrobial compounds. J. Chem. Inf. Model. 46, 2167–2182.

    Article  CAS  PubMed  Google Scholar 

  84. Karakoc, E., Cherkasov, A., and Sahinalp, S.C. (2006) Distance based algorithms for small biomolecule classification and structural similarity search. Bioinformatics 15, 243–251.

    Article  Google Scholar 

  85. Molecular Operational Environment. (2004) Chemical Computation Group Inc., Montreal, Canada.

    Google Scholar 

  86. SNNS: Stuttgart Neural Network Simulator, version 4.2, from University of Tübingen, Stuttgart, Germany. Available at http://www-ra.informatik.uni-tuebingen.de/SNNS/.

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Hilpert, K., Fjell, C.D., Cherkasov, A. (2008). Short Linear Cationic Antimicrobial Peptides: Screening, Optimizing, and Prediction. In: Otvos, L. (eds) Peptide-Based Drug Design. Methods In Molecular Biology™, vol 494. Humana Press. https://doi.org/10.1007/978-1-59745-419-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-419-3_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-990-1

  • Online ISBN: 978-1-59745-419-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics