Skip to main content
SpringerLink
Log in
Book cover

Computational Peptidology pp 43–66Cite as

Improved Methods for Classification, Prediction, and Design of Antimicrobial Peptides

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1268))

Abstract

Peptides with diverse amino acid sequences, structures, and functions are essential players in biological systems. The construction of well-annotated databases not only facilitates effective information management, search, and mining but also lays the foundation for developing and testing new peptide algorithms and machines. The antimicrobial peptide database (APD) is an original construction in terms of both database design and peptide entries. The host defense antimicrobial peptides (AMPs) registered in the APD cover the five kingdoms (bacteria, protists, fungi, plants, and animals) or three domains of life (bacteria, archaea, and eukaryota). This comprehensive database (http://aps.unmc.edu/AP) provides useful information on peptide discovery timeline, nomenclature, classification, glossary, calculation tools, and statistics. The APD enables effective search, prediction, and design of peptides with antibacterial, antiviral, antifungal, antiparasitic, insecticidal, spermicidal, anticancer activities, chemotactic, immune modulation, or antioxidative properties. A universal classification scheme is proposed herein to unify innate immunity peptides from a variety of biological sources. As an improvement, the upgraded APD makes predictions based on the database-defined parameter space and provides a list of the sequences most similar to natural AMPs. In addition, the powerful pipeline design of the database search engine laid a solid basis for designing novel antimicrobials to combat resistant superbugs, viruses, fungi, or parasites. This comprehensive AMP database is a useful tool for both research and education.

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

eBook
USD   39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   54.99
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. Zasloff M (2002) Antimicrobial peptides of multicellullar organisms. Nature 415:359–365

    Article  Google Scholar 

  2. Lehrer RI (2007) Multispecific myeloid defensins. Curr Opin Hematol 14:16–21

    Article  CAS  PubMed  Google Scholar 

  3. Boman HG (2003) Antibacterial peptides: basic facts and emerging concepts. J Intern Med 254:197–215

    Article  CAS  PubMed  Google Scholar 

  4. Hancock RE, Sahl HG (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557

    Article  CAS  PubMed  Google Scholar 

  5. Lai Y, Gallo RL (2009) AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30:131–141

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Wang G (ed) (2010) Antimicrobial peptides: discovery, design and novel therapeutic strategies. CABI, Oxfordshire, UK

    Google Scholar 

  7. Steiner H, Hultmark D, Engström Å, Bennich H, Boman HG (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature 292:246–248

    Article  CAS  PubMed  Google Scholar 

  8. Selsted ME, Harwig SS, Ganz T, Schilling JW, Lehrer RI (1985) Primary structures of three human neutrophil defensins. J Clin Invest 76:1436–1439

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Zasloff M (1987) Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor. Proc Natl Acad Sci U S A 84:5449–5453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Wang Z, Wang G (2004) APD: the antimicrobial peptide database. Nucleic Acids Res 32:D590–D592

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Wang G, Li X, Wang Z (2009) The updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933–D937

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Tossi A, Sandri L (2002) Molecular diversity in gene-coded, cationic antimicrobial polypeptides. Curr Pharm Des 8:743–761

    Article  CAS  PubMed  Google Scholar 

  13. Brahmachary M, Krishnan SP, Koh JL, Khan AM, Seah SH, Tan TW, Brusic V, Bajic VB (2004) ANTIMIC: a database of antimicrobial sequences. Nucleic Acids Res 32:D586–D589

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Seshadri Sundararajan V, Gabere MN, Pretorius A, Adam S, Christoffels A, Lehväslaiho M, Archer JA, Bajic VB (2012) DAMPD: a manually curated antimicrobial peptide database. Nucleic Acids Res 40:D1108–D1112

    Article  PubMed Central  PubMed  Google Scholar 

  15. Gueguen Y, Garnier J, Robert L, Lefranc MP, Mougenot I, de Lorgeril J, Janech M, Gross PS, Warr GW, Cuthbertson B, Barracco MA, Bulet P, Aumelas A, Yang Y, Bo D, Xiang J, Tassanakajon A, Piquemal D, Bachère E (2006) PenBase, the shrimp antimicrobial peptide penaeidin database: sequence-based classification and recommended nomenclature. Dev Comp Immunol 30:283–288

    Article  CAS  PubMed  Google Scholar 

  16. Seebah S, Suresh A, Zhou S, Choong YH, Chua H, Chuon D, Beuerman R, Verma C (2007) Defensins knowledgebase: a manually curated database and information source focused on the defensins family of antimicrobial peptides. Nucleic Acids Res 35:D265–D268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Hammami R, Zouhir A, Ben Hamida J, Fliss I (2007) BACTIBASE: a new web-accessible database for bacteriocin characterization. BMC Microbiol 7:89

    Article  PubMed Central  PubMed  Google Scholar 

  18. Wang CK, Kaas Q, Chiche L, Craik DJ (2008) Cybase: a database of cyclic protein sequences and structures, with applications in protein discovery and engineering. Nucleic Acids Res 36:D206–D210

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Hammami R, Ben Hamida J, Vergoten G, Fliss I (2009) PhytAMP: a database dedicated to antimicrobial plant peptides. Nucleic Acids Res 37:D963–D968

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Li Y, Chen Z (2008) RAPD: a database of recombinantly-produced antimicrobial peptides. FEMS Microbiol Lett 289:126–129

    Article  CAS  PubMed  Google Scholar 

  21. de Jong A, van Heel AJ, Kok J, Kuipers OP (2010) BAGEL2: mining for bacteriocins in genomic data. Nucleic Acids Res 38:W647–W651

    Article  PubMed Central  PubMed  Google Scholar 

  22. Novković M, Simunić J, Bojović V, Tossi A, Juretić D (2012) DADP: the database of anuran defense peptides. Bioinformatics 28:1406–1407

    Article  PubMed  Google Scholar 

  23. Li J, Qu X, He X, Duan L, Wu G, Bi D, Deng Z, Liu W, Ou HY (2012) ThioFinder: a web-based tool for the identification of thiopeptide gene clusters in DNA sequences. PLoS One 7:e45878

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Fjell CD, Hancock RE, Cherkasov A (2007) AMPer: a database and an automated discovery tool for antimicrobial peptides. Bioinformatics 23:1148–1155

    Article  CAS  PubMed  Google Scholar 

  25. Wade D, Englund J (2002) Synthetic antibiotic peptides database. Protein Pept Lett 9:53–57

    Article  CAS  PubMed  Google Scholar 

  26. Whitmore L, Wallace BA (2004) The Peptaibol Database: a database for sequences and structures of naturally occurring peptaibols. Nucleic Acids Res 32:D593–D594

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Wu H, Lu H, Huang J, Li G, Huang Q (2012) EnzyBase: a novel database for enzybiotic studies. BMC Microbiol 12:54

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Theolier J, Fliss I, Jean J, Hammami R (2013) MilkAMP: a comprehensive database of antimicrobial peptides of dairy origin. Dairy Sci Technol 94:181–193

    Article  Google Scholar 

  29. Thomas S, Karnik S, Barai RS, Jayaraman VK, Idicula-Thomas S (2010) CAMP: a useful resource for research on antimicrobial peptides. Nucleic Acids Res 38:D774–D780

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Piotto SP, Sessa L, Concilio S, Iannelli P (2012) YADAMP: yet another database of antimicrobial peptides. Int J Antimicrob Agents 39:346–351

    Article  CAS  PubMed  Google Scholar 

  31. Zhao X, Wu H, Lu H, Li G, Huang Q (2013) LAMP: a database linking antimicrobial peptides. PLoS One 8:e66557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Wu CH, Apweiler R, Bairoch A, Natale DA, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Mazumder R, O’Donovan C, Redaschi N, Suzek B (2006) The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res 34:D187–D191

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Rose PW, Bi C, Bluhm WF, Christie CH, Dimitropoulos D, Dutta S, Green RK, Goodsell DS, Prlic A, Quesada M, Quinn GB, Ramos AG, Westbrook JD, Young J, Zardecki C, Berman HM, Bourne PE (2013) The RCSB Protein Data Bank: new resources for research and education. Nucleic Acids Res 41:D475–D482

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Wheeler DL, Church DM, Lash AE, Leipe DD, Madden TL, Pontius JU, Schuler GD, Schriml LM, Tatusova TA, Wagner L, Rapp BA (2002) Database resources of the National Center for Biotechnology Information: 2002 update. Nucleic Acids Res 30:13–16

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Whittaker RH (1969) New concepts of kingdoms of organisms. Science 163:150–160

    Article  CAS  PubMed  Google Scholar 

  36. Woese CR, Fox GE (1977) Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc Natl Acad Sci U S A 74:5088–5090

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Wang G (2012) Chemical modifications of natural antimicrobial peptides and strategies for peptide engineering. Curr Biotechnol 1:72–79

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Epand RM, Vogel HJ (1999) Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta 1462:11–28

    Article  CAS  PubMed  Google Scholar 

  39. Klaenhammer TR (1993) Genetics of bacteriocins produced by lactic acid bacteria. FEMS Microbiol Rev 12:39–85

    Article  CAS  PubMed  Google Scholar 

  40. Duquesne S, Destoumieux-Garzón D, Peduzzi J, Rebuffat S (2007) Microcins, gene-encoded antibacterial peptides from enterobacteria. Nat Prod Rep 24:708–734

    Article  CAS  PubMed  Google Scholar 

  41. Egorov TA, Odintsova TI, Pukhalsky VA, Grishin EV (2005) Diversity of wheat anti-microbial peptides. Peptides 26:2064–2073

    Article  CAS  PubMed  Google Scholar 

  42. Bulet P, Stocklin R (2005) Insect antimicrobial peptides: structures, properties and gene regulation. Protein Pept Lett 12:3–11

    Article  CAS  PubMed  Google Scholar 

  43. Conlon JM (2008) Reflections on a systematic nomenclature for antimicrobial peptides from the skins of frogs of the family Ranidae. Peptides 29:1815–1819

    Article  CAS  PubMed  Google Scholar 

  44. Lata S, Sharma BK, Raghava GP (2007) Analysis and prediction of antibacterial peptides. BMC Bioinformatics 8:263

    Article  PubMed Central  PubMed  Google Scholar 

  45. Xiao X, Wang P, Lin WZ, Jia JH, Chou KC (2013) iAMP-2L: a two-level multi-label classifier for identifying antimicrobial peptides and their functional types. Anal Biochem 436:168–177

    Article  CAS  PubMed  Google Scholar 

  46. Wang G (2013) Database-guided discovery of potent peptides to combat HIV-1 or superbugs. Pharmaceuticals 6:728–758

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. O’Shea EF, O’Connor PM, O’Sullivan O, Cotter PD, Ross RP, Hill C (2013) Bactofencin a, a new type of cationic bacteriocin with unusual immunity. MBio 4:e00498–13

    PubMed Central  PubMed  Google Scholar 

  48. Menousek J, Mishra B, Hanke ML, Heim CE, Kielian T, Wang G (2012) Database screening and in vivo efficacy of antimicrobial peptides against methicillin-resistant Staphylococcus aureus USA300. Int J Antimicrob Agents 39:402–406

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Wang G, Watson KM, Peterkofsky A, Buckheit RW Jr (2010) Identification of novel human immunodeficiency virus type 1 inhibitory peptides based on the antimicrobial peptide database. Antimicrob Agents Chemother 54:1343–1346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Loose C, Jensen K, Rigoutsos I, Stephanopoulos G (2006) A linguistic model for the rational design of antimicrobial peptides. Nature 443:867–869

    Article  CAS  PubMed  Google Scholar 

  51. Lam KS, Salmon SE, Hersh EM, Hruby VJ, Kazmierski WM, Knapp RJ (1991) A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354:82–84

    Article  CAS  PubMed  Google Scholar 

  52. Cherkasov A, Hilpert K, Jenssen H, Fjell CD, Waldbrook M, Mullaly SC, Volkmer R, Hancock RE (2008) Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs. ACS Chem Biol 4:65–74

    Article  Google Scholar 

  53. Mishra B, Wang G (2012) The importance of amino acid composition in natural AMPs: an evolutional, structural, and functional perspective. Front Immunol 3:221

    Article  PubMed Central  PubMed  Google Scholar 

  54. Mishra B, Wang G (2012) Ab initio design of potent anti-MRSA peptides based on database filtering technology. J Am Chem Soc 134:12426–12429

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Wang G (2008) Structures of human host defense cathelicidin LL-37 and its smallest antimicrobial peptide KR-12 in lipid micelles. J Biol Chem 283:32637–32643

    Article  CAS  PubMed  Google Scholar 

  56. Saether O, Craik DJ, Campbell ID, Sletten K, Juul J, Norman DG (1995) Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. Biochemistry 34:4147–4158

    Article  CAS  PubMed  Google Scholar 

  57. Bauer F, Schweimer K, Klüver E, Conejo-Garcia JR, Forssmann WG, Rösch P, Adermann K, Sticht H (2001) Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity. Protein Sci 10:2470–2479

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Rozek A, Friedrich CL, Hancock RE (2000) Structure of the bovine antimicrobial peptide indolicidin bound to dodecylphosphocholine and sodium dodecyl sulfate micelles. Biochemistry 39:15765–15774

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the NIH (1R01AI105147-01A1, 1R56AI105147-01) and the State of Nebraska. The author thanks Zhe Wang for programming the original database and Biswajit Mishra for conducting the ab initio design of novel antimicrobials.

Author information

Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE, 68198-6495, USA

    Guangshun Wang Ph.D.

Authors
  1. Guangshun Wang Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guangshun Wang Ph.D. .

Editor information

Editors and Affiliations

  1. Center of Bioinformatics (COBI), School of Life Science and Technology, University of Electronic Science and Technology of China (UESTC), Chengdu, China

    Peng Zhou

  2. Center of Bioinformatics (COBI), School of Life Science and Technology, University of Electronic Science and Technology of China (UESTC), Chengdu, China

    Jian Huang

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Wang, G. (2015). Improved Methods for Classification, Prediction, and Design of Antimicrobial Peptides. In: Zhou, P., Huang, J. (eds) Computational Peptidology. Methods in Molecular Biology, vol 1268. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2285-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2285-7_3

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2284-0

  • Online ISBN: 978-1-4939-2285-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation