Skip to main content
SpringerLink
Log in

Knowledge-based computational methods for identifying or designing novel, non-homologous antimicrobial peptides

  • Review
  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

We describe computational approaches for identifying promising lead candidates for the development of peptide antibiotics, in the context of quantitative structure–activity relationships (QSAR) studies for this type of molecule. A first approach deals with predicting the selectivity properties of generated antimicrobial peptide sequences in terms of measured therapeutic indices (TI) for known antimicrobial peptides (AMPs). Based on a training set of anuran AMPs, the concept of sequence moments was used to construct algorithms that could predict TIs for a second test set of natural AMPs and could also predict the effect of point mutations on TI values. This approach was then used to design peptide antibiotics (adepantins) not homologous to known natural or synthetic AMPs. In a second approach, many novel putative AMPs were identified from DNA sequences in EST databases, using the observation that, as a rule, specific subclasses of highly conserved signal peptides are associated exclusively with AMPs. Both anuran and teleost sequences were used to elucidate this observation and its implications. The predicted therapeutic indices of identified sequences could then be used to identify new types of selective putative AMPs for future experimental verification.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bechinger B, Zasloff M, Opella SJ (1998) Structure and dynamic of the antibiotic peptide PGLa in membranes by solution and solid-state nuclear magnetic resonance technology. Biophys J 74:981–987

    Article  PubMed  CAS  Google Scholar 

  • Bessalle R, Haas H, Goria A, Shalit I, Fridkin M (1992) Augmentation of the antibacterial activity of magainin by positive-charge chain extension. Antimicrob Agents Chemother 36:313–317

    PubMed  CAS  Google Scholar 

  • Bhonsle JB, Venugopal D, Huddler DP, Magill AJ, Hicks RP (2007) Application of 3D-QSAR for identification of descriptors defining bioactivity of antimicrobial peptides. J Med Chem 50:6545–6553

    Article  PubMed  CAS  Google Scholar 

  • Bolintineanu D, Hazrati E, Davis HT, Lehrer RI, Kaznessis YN (2010) Antimicrobial mechanism of pore-forming protegrin peptides: 100 pores to kill E. coli. Peptides 31:1–8

    Article  PubMed  CAS  Google Scholar 

  • Boman HG, Wade D, Boman IA, Wihlint B, Merrifield RB (1989) Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids. FEBS Lett 259:103–106

    Article  PubMed  CAS  Google Scholar 

  • Bommarius B, Kalman D (2009) Antimicrobial and host defense peptides for therapeutic use against multidrug-resistant pathogens: new hope on the horizon. IDrugs 12:376–380

    PubMed  CAS  Google Scholar 

  • Bowdish DME, Davidson DJ, Monisha G, Scott MG, Hancock REW (2005) Immunomodulatory activities of small host defense peptides. Antimicrob Agents Chemother 49:1727–1732

    Article  PubMed  CAS  Google Scholar 

  • Brogden KA (2005) Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria. Nat Rev Microbiol 3:238–250

    Article  PubMed  CAS  Google Scholar 

  • Castro MS, Cilli EM, Fontes W (2006) Combinatorial synthesis and directed evolution applied to the production of α-helix forming antimicrobial peptides analogues. Curr Protein Pept Sci 7:473–478

    Article  PubMed  CAS  Google Scholar 

  • Chekmenov EY, Vollmar BS, Cottem M (2010) Can antimicrobial peptides scavenge around a cell in less than a second. Biochim Biophys Acta 1798:228–234

    Article  CAS  Google Scholar 

  • Chen F-Y, Lee M-T, Huang HW (2003) Evidence for membrane thinning effect as the mechanism for peptide-induced pore formation. Biophys J 84:3751–3758

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Vasil AI, Rehaume L, Mant CT, Burns JL, Vasil ML, Hancock REW, Hodges RS (2006) Comparison of biophysical and biologic properties of α-helical enantiomeric antimicrobial peptides. Chem Biol Drug Des 67:162–173

    Article  PubMed  CAS  Google Scholar 

  • Chen LF, Chopra T, Kave KS (2009) Pathogens resistant to antimicrobial agents. Infect Dis Clin North Am 23:817–845

    Article  PubMed  Google Scholar 

  • Conlon JM, Sonnevend A, Davidson C, Smith DD, Nielsen PF (2004) The ascaphins: a family of antimicrobial peptides from the skin secretions of the most primitive extant frog, Ascaphus truei. Biochem Biophys Res Commun 320:170–175

    Article  PubMed  CAS  Google Scholar 

  • Conlon JM, Galadari S, Raza H, Condamine E (2008) Design of potent non-toxic antimicrobial agents based upon the naturally occurring frog skin peptides, ascaphin 8 and peptide XT-7. Chem Biol Drug Des 72:58–64

    Article  PubMed  CAS  Google Scholar 

  • Conlon JM, Kolodziejek J, Nowotny N (2009) Antimicrobial peptides from the skins of North American frogs. Biochim Biophys Acta 1788:1556–1563

    Article  PubMed  CAS  Google Scholar 

  • Conticello SG, Gilad Y, Avidan N, Ben-Asher E, Levy Z, Fainzilber M (2001) Mechanisms for evolving hypervariability: the case of conopeptides. Mol Biol Evol 18:120–131

    PubMed  CAS  Google Scholar 

  • Cuthbertson JM, Doyle DA, Sansom MSP (2005) Transmembrane helix prediction: a comparative evaluation and analysis. Protein Eng Des Select 18:295–308

    Article  CAS  Google Scholar 

  • Dathe M, Nikolenko H, Meyer J, Beyermann M, Bienert M (2001) Optimization of the antimicrobial activity of magainin peptides by modification of charge. FEBS Lett 501:146–150

    Article  PubMed  CAS  Google Scholar 

  • Desbois AP, Gemmell CG, Coote PJ (2010) In vivo efficacy of the antimicrobial peptide ranalexin in combination with the endopeptidase lysostaphin against wound and systemic meticillin-resistant Staphylococcus aureus (MRSA) infections. Int J Antimicrob Agents 35:559–565

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg D, Weiss RM, Terwilliger CT, Wilcox W (1982) Hydrophobic moments and protein structure. Faraday Symp Chem Soc 17:109–120

    Article  Google Scholar 

  • El Amri C, Nicolas P (2008) Plasticins: membrane-damaging peptides with “chameleon-like” properties. Cell Mol Life Sci 65:895–909

    Article  PubMed  CAS  Google Scholar 

  • El Amri C, Bruston F, Joanne P, Lacombe C, Nicolas P (2007) Intrinsic flexibility and structural adaptability of plasticins membrane-damaging peptides as a strategy for functional versatility. Eur Biophys J 36:901–909

    Article  PubMed  CAS  Google Scholar 

  • Epand RF, Maloy WL, Ramamoorthy A, Epand RM (2010) Probing the „charge cluster mechanism” in amphipathic helical cationic antimicrobial peptides. Biochemistry 49:4076–4084

    Article  PubMed  CAS  Google Scholar 

  • Fernandez DI, Gehman JD, Separovic F (2009) Membrane interactions of antimicrobial peptides from Australian frogs. Biochim Biophys Acta 1788:1630–1638

    Article  PubMed  CAS  Google Scholar 

  • Ferre R, Melo MN, Correia AD, Feliu L, Bardají E, Planas M, Castanho M (2009) Synergistic effects of the membrane actions of cecropin-melittin antimicrobial hybrid peptide BP100. Biophys J 96:1815–1827

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Fjell CD, Jenssen H, Hilpert K, Cheung WA, Panté N, Hancock REW, Cherkasov A (2009) Identification of novel antibacterial peptides by chemoinformatics and machine learning. J Med Chem 52:2006–2015

    Article  PubMed  CAS  Google Scholar 

  • Frecer V, Ho B, Ding JL (2004) De novo design of potent antimicrobial peptides. Antimicrob Agents Chemother 48:3349–3357

    Article  PubMed  CAS  Google Scholar 

  • Fukuoka S, Howe J, Andrä J, Gutsmann T, Rössle M, Brandenburg K (2008) Physico-chemical and biophysical study of the interaction of hexa- and heptaacyl lipid A from Erwinia carotovora with magainin 2-derived antimicrobial peptides. Biochim Biophys Acta 1778:2051–2057

    Article  PubMed  CAS  Google Scholar 

  • Giangaspero A, Sandri L, Tossi A (2001) Amphipathic α-helical antimicrobial peptides. A systematic study of the effects of structural and physical properties on biological activity. Eur J Biochem 268:5589–5600

    Article  PubMed  CAS  Google Scholar 

  • Gibson BW, Tang D, Mandrell R, Kelly M, Spindel ER (1991) Bombinin-like peptides with antimicrobial activity from skin secretions of the Asian toad, Bombina orientalis. J Biol Chem 266:23103–23111

    PubMed  CAS  Google Scholar 

  • Glukhov E, Stark M, Burrows LL, Deber CM (2005) Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes. J Biol Chem 280:33960–33967

    Article  PubMed  CAS  Google Scholar 

  • Gottler LM, Ramamoorthy A (2009) Structure, membrane orientation, mechanism, and function of pexiganan—A highly potent antimicrobial peptide designed from magainin. Biochim Biophys Acta 1788:1680–1686

    Article  PubMed  CAS  Google Scholar 

  • Grage SL, Afonin S, Urlich AS (2010) Dynamic transitions of membrane-active peptides. Methods Mol Biol 618:183–207

    Article  PubMed  CAS  Google Scholar 

  • Guy HR (1985) Amino acid side-chain partition energies and distribution of residues in soluble proteins. Biophys J 47:61–70

    Article  PubMed  CAS  Google Scholar 

  • Hancock REW (2001) Cationic peptides: effectors in innate immunity and novel antimicrobials. Lancet Infect Dis 1:156–164

    Article  PubMed  CAS  Google Scholar 

  • Hancock REW, Lehrer R (1998) Cationic peptides: a new source of antibiotics. Trends Biotechnol 16:82–88

    Article  PubMed  CAS  Google Scholar 

  • Hancock REW, Sahl H-G (2006) Antimicrobial and host defense peptides as new anti-infective therapeutic strategies. Nat Biotechnol 24:1551–1557

    Article  PubMed  CAS  Google Scholar 

  • Haney EF, Hunter HN, Matsuzaki K, Vogel HJ (2009) Solution NMR studies of amphibian antimicrobial peptides: linking structure to function? Biochim Biophys Acta 1788:1639–1655

    Article  PubMed  CAS  Google Scholar 

  • Hawrani A, Howe RA, Walsh TR, Dempsey CE (2008) Origin of low mammalian cell toxicity in a class of highly active antimicrobial amphipathic helical peptides. J Biol Chem 283:18636–18645

    Article  PubMed  CAS  Google Scholar 

  • Hilpert K, Fjell CD, Cherkasov A (2008) Short linear cationic antimicrobial peptides: screening optimizing and prediction. Methods Mol Biol 494:127–159

    Article  PubMed  CAS  Google Scholar 

  • Huang HW (2000) Action of antimicrobial peptides: two state model. Biochemistry 39:8347–8352

    Article  PubMed  CAS  Google Scholar 

  • Imura Y, Choda N, Matsuzaki K (2008) Magainin 2 in action: distinct modes of membrane permeabilization in living bacterial and mammalian cells. Biophys J 95:5757–5765

    Article  PubMed  Google Scholar 

  • Islam K, Hawser SP (1998) MSI-78 (Magainin Pharmaceuticals). IDrugs 1:605–609

    PubMed  CAS  Google Scholar 

  • Jang H, Ma B, Woolf TB, Nussinov R (2006) Interaction of protegrin-1 with lipid bilayers: membrane thinning effect. Biophys J 91:2848–2859

    Article  PubMed  CAS  Google Scholar 

  • Janin J (1979) DeltaG-transfer from buried interior to solvent accessible surface. Nature 277:491–492

    Article  PubMed  CAS  Google Scholar 

  • Jiang Z, Vasil AI, Hale J, Hancock REW, Vasil ML, Hodges RS (2008) Effects of net charge and the number of positively charged residues on the biological activity of amphipathic α-helical cationic antimicrobial peptides. Biopolymers 90:369–383

    Article  PubMed  CAS  Google Scholar 

  • Jin Y, Mozsolits H, Hammer J, Zmuda E, Zhu F, Zhang Y, Aguilar MI, Blazyk J (2003) Influence of tryptophan on lipid binding of linear amphipathic cationic antimicrobial peptides. Biochemistry 42:9395–9405

    Article  PubMed  CAS  Google Scholar 

  • Juretić D (1990) Antimicrobial peptides of the magainin family: membrane depolarization studies on E. coli and cytochrome oxidase liposomes. Stud Biophys 138:79–86

    Google Scholar 

  • Juretić D, Lučin A (1998) The preference functions method for predicting helical turns with membrane propensity. J Chem Inf Comput Sci 38:575–585

    Article  Google Scholar 

  • Juretić D, Zoranić L, Zucić D (2002) Basic charge clusters and predictions of membrane protein topology. J Chem Inf Comput Sci 42:620–632

    Article  PubMed  CAS  Google Scholar 

  • Juretić D, Jerončić A, Zucić D (1999) Sequence analysis of membrane proteins with the web server SPLIT. Croat Chem Acta 72:975–997

    Google Scholar 

  • Juretić D, Vukičević D, Ilić N, Antcheva N, Tossi A (2009) Computational design of highly selective antimicrobial Peptides. J Chem Inf Model 49:2873–2882

    Article  PubMed  CAS  Google Scholar 

  • Klein E, Smith DL, Laxminarayan R (2007) Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999–2005. Emerg Infect Dis 13:1840–1846

    PubMed  Google Scholar 

  • Kondejewski LH, Jelokhani-Niaraki M, Farmer SW, Lix B, Kay CM, Sykes BD, Hancock REW, Hodges RS (1999) Dissociation of antimicrobial and hemolytic activities in cyclic peptide diastereomers by systematic alterations in amphipathicity. J Biol Chem 274:13181–13192

    Article  PubMed  CAS  Google Scholar 

  • Konig E, Bininda-Emonds OR (2011) Evidence for convergent evolution in the antimicrobial peptide system in anuran amphibians. Peptides 32:20–25

    Google Scholar 

  • Kragol G, Lovas S, Varadi G, Condie BA, Hoffmann R, Otvos L Jr (2001) The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry 40:3016–3026

    Article  PubMed  CAS  Google Scholar 

  • Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157:105–132

    Article  PubMed  CAS  Google Scholar 

  • La Rocca P, Biggin PC, Tieleman DP, Sanson MS (1999) Simulation studies of the interaction of antimicrobial peptides and lipid bilayers. Biochim Biophys Acta 1462:185–200

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Langham AA, Khandelia H, Schuster B, Waring AJ, Lehrer RI, Kaznessis YN (2008) Correlation between simulated physicochemical properties and hemolycity of protegrin-like antimicrobial peptides: Predicting experimental toxicity. Peptides 29:1085–1093

    Article  PubMed  CAS  Google Scholar 

  • Lauth X, Shike H, Burns JC, Westerman ME, Ostland VE, Carlberg JM, Van Olst JC, Nizet V, Taylor SW, Shimizu C, Bulet P (2002) Discovery and characterization of two isoforms of moronecidin, a novel antimicrobial peptide from hybrid striped bass. J Biol Chem 277:5030–5039

    Article  PubMed  CAS  Google Scholar 

  • Lejon T, Stiberg T, Strøm MB, Svendsen JS (2004) Prediction of antibiotic activity and synthesis of new pentadecapeptides based on lactoferricins. J Pept Sci 10:329–335

    Article  PubMed  CAS  Google Scholar 

  • Li Y-D, Xie Z-Y, Du Y-L, Zhou Z, Mao X-M, Lv L-X, Li Y-Q (2009) The rapid evolution of signal peptides is mainly caused by relaxed selection on non-synonymous and synonymous sites. Gene 436:8–11

    Article  PubMed  CAS  Google Scholar 

  • Lohner K, Prossnigg F (2009) Biological activity and structural aspects of PGLa interaction with membrane mimetic systems. Biochim Biophys Acta 1788:1656–1666

    Article  PubMed  CAS  Google Scholar 

  • Maloy WL, Kari UP (1995) Structure-activity studies on magainins and other host defense peptides. Biopolymers 37:105–122

    Article  PubMed  CAS  Google Scholar 

  • Marr AK, Gooderham WJ, Hancock REW (2006) Antimicrobial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol 6:468–472

    Article  PubMed  CAS  Google Scholar 

  • Mason AJ, Bechinger B, Kichler A (2007) Rational design of vector and antibiotic peptides using solid-state NMR. Mini-Rev Med Chem 7:491–497

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki K (1998) Magainins as paradigm for the mode of action of pore forming polypeptides. Biochim Biophys Acta 1376:391–400

    PubMed  CAS  Google Scholar 

  • Matsuzaki K (2009) Control of cell selectivity of antimicrobial peptides. Biochim Biophys Acta 1788:1687–1692

    Article  PubMed  CAS  Google Scholar 

  • Matsuzaki K, Murase O, Fujii N, Miyajima K (1995) Translocation of a channel-forming antimicrobial peptide, magainin 2, across lipid bilayers by forming a pore. Biochemistry 34:6521–6526

    Article  PubMed  CAS  Google Scholar 

  • Mattute B, Knoop FC, Conlon JM (2000) Kassinatuerin-1: a peptide with broadspectrum antimicrobial activity isolated from the skin of the hyperoliid frog, Kassina senegalensis. Biochem Biophys Res Commun 268:433–436

    Article  PubMed  CAS  Google Scholar 

  • Melnyk RA, Kim S, Curran AR, Engelman DM, Bowie JU, Deber CM (2004) The affinity of GXXXG motifs in transmembrane helix-helix interactions is modulated by long-range communication. J Biol Chem 279:16591–16597

    Article  PubMed  CAS  Google Scholar 

  • Mihajlovic M, Lazarides T (2010) Antimicrobial peptides bind more strongly to membrane pores. Biochim Biophys Acta 1798:1494–1502

    Article  PubMed  CAS  Google Scholar 

  • Nicolas P (2009) Multifunctional host defense peptides: intracellular targeting antimicrobial peptides. FEBS J 276:6483–6496

    Article  PubMed  CAS  Google Scholar 

  • Nicolas P, El Amri C (2009) The dermaseptin superfamily: a gene-based combinatorial library of antimicrobial peptides. Biochim Biophys Acta 1788:1537–1550

    Article  PubMed  CAS  Google Scholar 

  • Norrby SR, Nord CE, Finch R (2005) Lack of development of new antimicrobial drugs: a potential serious threat to public health. Lancelet Infect Dis 5:115–119

    Google Scholar 

  • Ostberg N, Kaznessis Y (2005) Protegrin structure–activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity. Peptides 26:197–206

    Article  PubMed  CAS  Google Scholar 

  • Pál T, Sonnevend A, Galadari S, Conlon JM (2005) Design of potent, non-toxic antimicrobial agents based upon the structure of the frog skin peptide, pseudin-2. Regul Pept 129:85–91

    Article  PubMed  CAS  Google Scholar 

  • Pál T, Abraham B, Sonnevend A, Jumaa P, Conlon JM (2006) Brevinin-1BYa: a naturally occurring peptide from frog skin with broad-spectrum antibacterial and antifungal properties. Int J Antimicrob Agents 27:525–529

    Article  PubMed  CAS  Google Scholar 

  • Pandey BK, Ahmad A, Asthana N, Azmi S, Srivastava RM, Srivastava S, Verma R, Vishwakarma AL, Ghosh JK (2010) Cell-selective lysis by novel analogues of melittin against human red blood cells and Escherichia coli. Biochemistry 49:7920–7929

    Article  PubMed  CAS  Google Scholar 

  • Pathak N, Salas-Auvert R, Ruche G, Janna M-H, McCarthy D, Harrison RG (1995) Comparison of the effect of hydrophobicity, amphiphilicity, and α-helicity on the activities of antimicrobial peptides. Proteins Struct Funct Genet 22:182–186

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Payá E, Houghten RA, Blondelle SE (1994) Determination of the secondary structure of selected melittin analogues with different haemolytic activities. Biochem J 299:587–591

    PubMed  Google Scholar 

  • Perron GG, Zasloff M, Bell G (2006) Experimental evolution of resistance to an antimicrobial peptide. Proc R Soc B 273:251–256

    Article  PubMed  CAS  Google Scholar 

  • Peschel A, Sahl HG (2006) The co-evolution of host cationic antimicrobial peptides and microbial resistance. Nat Rev Microbiol 4:529–536

    Article  PubMed  CAS  Google Scholar 

  • Ramamoorthy A (2009) Beyond NMR spectra of antimicrobial peptides: dynamical images at atomic resolution and functional insights. Solid State Nucl Magn Reson 35:201–207

    Article  PubMed  CAS  Google Scholar 

  • Rockström J, Steffen W, Noone K, Persson A, Chapin FS 3rd, Lambin EF, Lenton TM, Scheffer M, Folke C, Schellnhuber HJ, Nykvist B, de Wit CA, Hughes T, van der Leeuw S, Rodhe H, Sörlin S, Snyder PK, Costanza R, Svedin U, Falkenmark M, Karlberg L, Corell RW, Fabry VJ, Hansen J, Walker B, Liverman D, Richardson K, Crutzen P, Foley JA (2009) A safe operating space for humanity. Nature 461:472–475

    Article  PubMed  CAS  Google Scholar 

  • Roelants K, Fry BG, Norman JA, Clynen E, Schoofs L, Bossuvt F (2010) Identical skin toxins by convergent molecular adaptation in frogs. Curr Biol 20:125–130

    Article  PubMed  CAS  Google Scholar 

  • Rollins-Smith LA (2009) The role of amphibian antimicrobial peptides in protection of amphibians from pathogens linked to global amphibian declines. Biochim Biophys Acta 1788:1593–1599

    Article  PubMed  CAS  Google Scholar 

  • Schneider D, Engelman DM (2004) Motifs of two small residues can assist but are not sufficient to mediate transmembrane helix interactions. J Mol Biol 343:799–804

    Article  PubMed  CAS  Google Scholar 

  • Senes A, Gerstein M, Engelman DM (2000) Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with β-branched residues at neighboring positions. J Mol Biol 296:921–936

    Article  PubMed  CAS  Google Scholar 

  • Sengupta D, Leontiadou H, Mark AE, Marrink SJ (2008) Toroidal pores formed by antimicrobial peptides show significant disorder. Biochim Biophys Acta 1778:2308–2317

    Article  PubMed  CAS  Google Scholar 

  • Siegal RE (2008) Emerging Gram-negative antibiotic resistance: daunting challenges, declining sensitivities and dire consequences. Respir Care 53:471–479

    Google Scholar 

  • Simmaco M, Mignogna G, Barra D (1998) Antimicrobial peptides from amphibian skin: what do they tell us? Biopolymers 47:435–450

    Article  PubMed  CAS  Google Scholar 

  • Simmaco M, Kreil G, Barra D (2009) Bombinins, antimicrobial peptides from Bombina species. Biochim Biophys Acta 1788:1551–1555

    Article  PubMed  CAS  Google Scholar 

  • Steinberg DA, Hurst MA, Fujii CA, Kung AH, Ho JF, Cheng FC, Loury DJ, Fiddes JC (1997) Protegrin-1: a broad-spectrum, rapidly microbicidal peptide with in vivo activity. Antimicrob Agents Chemother 41:1738–1742

    PubMed  CAS  Google Scholar 

  • Strandberg E, Kanithasen N, Tiltak D, Bürck J, Wadhwani P, Zwernemann O, Urlich AC (2008) Solid-state NMR analysis comparing the designer made antibiotic MSI-103 with its parent peptide PGLa in lipid bilayers. Biochemistry 47:2601–2616

    Article  PubMed  CAS  Google Scholar 

  • Strandberg E, Esteban-Martín S, Salgado J, Ulrich AS (2009a) Orientation and dynamics of peptides in membranes calculated from 2H-NMR data. Biophys J 96:3223–3232

    Article  PubMed  CAS  Google Scholar 

  • Strandberg E, Tremouilhac P, Wadhwani P, Urlich AS (2009b) Synergistic transmembrane insertion of the heterodimeric PGLa/magainin 2 complex studied by solid-state NMR. Biochim Biophys Acta 1788:1667–1679

    Article  PubMed  CAS  Google Scholar 

  • Stuart SN, Chanson JS, Cox NA, Young BE, Rodrigues AS, Fischman DL, Waller RW (2004) Status and trends of amphibian declines and extinctions worldwide. Science 306:1783–1786

    Article  PubMed  CAS  Google Scholar 

  • Sun X, Chen S, Li S, Yan H, Fan Y, Mi H (2005) Deletion of two C-terminal Gln residues of 12–26-residue fragment of melittin improves its antimicrobial activity. Peptides 26:369–375

    Article  PubMed  CAS  Google Scholar 

  • Taboureau O (2010) Methods for building quantitative structure-activity relationship (QSAR) descriptors and predictive models for computer-aided design of antimicrobial peptides. Methods Mol Biol 618:77–86

    Article  PubMed  CAS  Google Scholar 

  • Taboureau O, Olsen OH, Nielsen JD, Raventos D, Mygind PH, Kristensen HH (2006) Design of novispirin antimicrobial peptides by quantitative structure-activity relationship. Chem Biol Drug Des 68:48–57

    Article  PubMed  CAS  Google Scholar 

  • Tachi T, Epand RF, Epand RM, Matsuzaki K (2002) Position dependent hydrophobicity of the antimicrobial magainin peptide affects the mode of peptide-lipid interactions and selective toxicity. Biochemistry 41:10723–10731

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Tossi A, Tarantino C, Romeo D (1997) Design of synthetic antimicrobial peptides based on sequence analogy and amphipathicity. Eur J Biochem 250:549–558

    Article  PubMed  CAS  Google Scholar 

  • Tossi A, Sandri L, Giangaspero A (2000) Amphipathic helical antimicrobial peptides. Biopolymers Peptide Sci 55:4–30

    Article  CAS  Google Scholar 

  • Tossi A, Sandri L, Giangaspero A (2002) New consensus hydrophobicity scale extended to non-proteinogenic amino acids. In: Benedetti E, Pedone C (eds) Peptides 2002, proceedings of the 27th European peptide symposium Sorrento August 31st–September 6th 2002. Edizioni Ziino, Napoli, pp 416–417

  • Tremouilhac P, Strandberg E, Wadhwani P, Ulrich AS (2006) Conditions affecting the re-alignment of the antimicrobial peptide PGLa in membranes as monitored by solid state 2H-NMR. Biochim Biophys Acta 1758:1330–1342

    Article  PubMed  CAS  Google Scholar 

  • Vanhoye D, Bruston F, Nicolas P, Amiche M (2003) Antimicrobial peptides from hylid and ranin frogs originated from a 150-million-year-old ancestral precursor with a conserved signal peptide but a hypermutable antimicrobial domain. Eur J Biochem 270:2068–2081

    Article  PubMed  CAS  Google Scholar 

  • Wade D, Andreu D, Mitchell SAN, Silveira AM, Boman A, Boman HG, Merrifield RB (1992) Antibacterial peptides designed as analogs or hybrids of cecropins and melittin. Int J Pept Protein Res 40:429–436

    Article  PubMed  CAS  Google Scholar 

  • Walters RFS, De Grado WF (2006) Helix-packing motifs in membrane proteins. Proc Natl Acad Sci USA 103:13658–13663

    Article  PubMed  CAS  Google Scholar 

  • Wang G, Li X, Wang Z (2009) APD2: the updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res 37:D933–D937

    Article  PubMed  CAS  Google Scholar 

  • Woodword N (1998) Glycopeptide-resistant enterococci: a decade of experience. J Med Microbiol 47:849–862

    Article  Google Scholar 

  • Yang N, Stensen W, Svendsen JV, Rekdal Ø (2002) Enhanced antitumor activity and selectivity of lactoferrin-derived peptides. J Pept Res 60:187–197

    Article  PubMed  CAS  Google Scholar 

  • Yeaman MR, Yount NY (2003) Mechanism of antimicrobial peptide action and resistance. Pharmacol Rev 55:27–55

    Article  PubMed  CAS  Google Scholar 

  • Yeaman MR, Yount NY (2007) Unifying themes in host defence effector polypeptides. Nat Rev Microbiol 5:727–740

    Article  PubMed  CAS  Google Scholar 

  • Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukocyte Biol 75:39–48

    Article  PubMed  CAS  Google Scholar 

  • Zasloff M (2002) Antimicrobial peptides of multicellular origin. Nature 415:389–395

    Article  PubMed  CAS  Google Scholar 

  • Zelezetsky I, Tossi A (2006) Alpha-helical antimicrobial peptides–using a sequence template to guide structure-activity relationship studies. Biochim Biophys Acta 1758:1436–1449

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Falla TJ (2010) Potential therapeutic application of host defense peptides. Methods Mol Biol 618:303–327

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was carried out as part of the Italy/Croatia Scientific and Technological Cooperation Programme, Project SV2. The work was supported in part by Croatian Ministry of Science, Education and Sport (Grant Nos. 177-1770495-0476 (D.J.), 098-1770495-2919 (B.L.), 177-0000000-0884 (D.V.) and 037-0000000-2779 (D.V.)), and by a Friuli Venezia Giulia LR26 grant for the R3A2 network project.

Author information

Authors and Affiliations

  1. Department of Physics, Faculty of Science, University of Split, 21000, Split, Croatia

    Davor Juretić & Nada Ilić

  2. Department of Mathematics, Faculty of Science, University of Split, 21000, Split, Croatia

    Damir Vukičević

  3. Laboratory of Computational Biophysics, Campus Vienna Biocenter 5, 1030, Vienna, Austria

    Dražen Petrov

  4. Mediterranean Institute for Life Sciences, 21000, Split, Croatia

    Mario Novković

  5. Interdisciplinary Centre for Advanced Science and Technology, University of Split, 21000, Split, Croatia

    Mario Novković

  6. Ruđer Bošković Institute, 10000, Zagreb, Croatia

    Viktor Bojović & Bono Lučić

  7. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy

    Alessandro Tossi

Authors
  1. Davor Juretić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Damir Vukičević
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dražen Petrov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario Novković
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Viktor Bojović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bono Lučić
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nada Ilić
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alessandro Tossi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Davor Juretić.

Additional information

Membrane-active peptides: 455th WE-Heraeus-Seminar and AMP 2010 Workshop.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Juretić, D., Vukičević, D., Petrov, D. et al. Knowledge-based computational methods for identifying or designing novel, non-homologous antimicrobial peptides. Eur Biophys J 40, 371–385 (2011). https://doi.org/10.1007/s00249-011-0674-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00249-011-0674-7

Keywords

Search

Navigation