Skip to main content
SpringerLink
Log in

Identifying therapeutic template by evaluating the structural stability of gram positive anti-bacterial peptides-a computational approach

  • Published:
Interdisciplinary Sciences: Computational Life Sciences Aims and scope Submit manuscript

Abstract

Clinically significant antibiotic resistance has evolved against virtually every antibiotic deployed. Yet the development of new classes of antibiotics has lagged far behind our growing need for such drugs. Antimicrobial peptides (AMPs) have emerged as novel therapeutics hailed for their bactericidal and immunomodulatory properties. However, the process of optimizing antimicrobial peptide stability, using large peptide libraries is both tedious and expensive. The intent of this study is to analyze computationally the stability of anti-bacterial peptides (ABPs), particularly Gram positive and to discover a potential template from a pool of ABPs for therapeutic use. Consequently we highlighted that MiAMP1 appears advantageous over the other ABPs with respect to stability, and may provide a convenient platform for the development of anti-bacterial therapeutic peptide.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Baker, E.N., Hubbard, R.E. 1984. Hydrogen bonding in globular proteins. Prog Biophys Mol Biol 44, 97–179.

    Article  PubMed  CAS  Google Scholar 

  2. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E. 2000. The Protein Data Bank. Nucleic Acids Res 28, 235–242.

    Article  PubMed  CAS  Google Scholar 

  3. Boman, H.G. 2003. Antibacterial peptides: Basic facts and emerging concepts. J Intern Med 254, 197–215.

    Article  PubMed  CAS  Google Scholar 

  4. Borg, M.A. 2003. Bed occupancy and overcrowding as determinant factors in the incidence of MRSA infections within general ward settings. J Hosp Infect 54, 316–318.

    Article  PubMed  CAS  Google Scholar 

  5. Brogden, K.A., Ackermann, M., McCray, P.B.J., Tack, B.F. 2003. Antimicrobial peptides in animals and their role in host defences. Int J Antimicrob Agents 22, 465–478.

    Article  PubMed  CAS  Google Scholar 

  6. Bulet, P., Stocklin, R., Menin, L. 2004. Anti-microbial peptides: From invertebrates to vertebrates. Immunol Rev 198, 169–184.

    Article  PubMed  CAS  Google Scholar 

  7. Burley, S.K., Petsko, G.A. 1986. Amino-aromatic interactions in proteins. FEBS Letters 203, 139–143.

    Article  PubMed  CAS  Google Scholar 

  8. Burley, S.K., Petsko, G.A. 1988. Weakly polar interactions in proteins. Adv Protein Chem 39, 125–189.

    Article  PubMed  CAS  Google Scholar 

  9. Davies, J. 1996. Bacteria on the rampage. Nature 383, 219–220.

    Article  PubMed  CAS  Google Scholar 

  10. Desiraju, G.R. 1991. TheC-H…O hydrogen bonding crystals: What is it? Acc Chem Res 24, 290–296.

    Article  CAS  Google Scholar 

  11. Dill, K.A. 1990. Dominant forces in protein folding. Biochemistry 29, 7133–7155.

    Article  PubMed  CAS  Google Scholar 

  12. Dosztanyi, Z., Fiser, A., Simon, I. 1997. Stabilization centers in proteins: Identification, characterization and predictions. J Mol Biol 272, 597–612.

    Article  PubMed  CAS  Google Scholar 

  13. Dosztanyi, Z.S., Magyar, C.S., Tusnady, E.G., Simon, I. 2003. SCide: Identification of stabilization centers in proteins. Bioinformatics 19, 899–900.

    Article  PubMed  CAS  Google Scholar 

  14. Enright, M.C. 2003. The evolution of a resistant pathogen — the case of MRSA. Curr Opin Pharmacol 3, 474–479.

    Article  PubMed  CAS  Google Scholar 

  15. Finlay, B.B., Hancock, R.E. 2004. Can innate immunity be enhanced to treat microbial infections? Nat Rev Microbiol 2, 497–504.

    Article  PubMed  CAS  Google Scholar 

  16. Gallivan, J.P., Dougherty, D.A. 1999. Cation-π interactions in structural biology. Proc Natl Acad Sci USA 96, 9459–9464.

    Article  PubMed  CAS  Google Scholar 

  17. Gallo, R.L., Kim, K.J., Bernfield, M. 1997. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J Biol Chem 272, 3088–3093.

    Google Scholar 

  18. Giuliani, A., Pirri, G., Nicoletto, S.F. 2007. Antimicrobial peptides: An overview of a promising class of therapeutics. Cen Eur J Biol 2, 1–33.

    Article  CAS  Google Scholar 

  19. Guex, N., Peitsch, M.C. 1997. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 18, 2714–2723.

    Article  PubMed  CAS  Google Scholar 

  20. Guruprasad, K., Reddy, B.V.B., Pandit, M.W. 1990. Correlation between stability of a protein and its dipeptide composition: A novel approach for predicting in vivo stability of a protein from its primary sequence. Protein Eng 4, 155–161.

    Article  PubMed  CAS  Google Scholar 

  21. Hamman, J.H., Enslin, G.M., Kotze, A.F. 2005. Oral delivery of peptide drugs: Barriers and developments. BioDrugs 19, 165–177.

    Article  PubMed  CAS  Google Scholar 

  22. Him, H.J., Steif, C., Vogl, T., Meyer, R., Renner, M., Ledermiiller, R. 1993. Fundamentals of protein stability. Pure & Appl Chern 65, 947–952.

    Article  Google Scholar 

  23. Janek, K., Rothemund, S., Gast, K., Beyermann, M., Zipper, J., Fabian, H., Bienert, M., Krause, E. 2001. Study of the conformational transition of A beta (1–42) using D-amino acid replacement analogues. Biochemistry 40, 5457–5463.

    Article  PubMed  CAS  Google Scholar 

  24. Jeffrey, G.A., Saenger, W. 1993. Hydrogen bonding in biological structures. Biophys J 64, 21–25.

    Google Scholar 

  25. Koczulla, A.R., Bals, R. 2003. Antimicrobial peptides — Current status and therapeutics potential. Drugs 63, 389–406.

    Article  PubMed  CAS  Google Scholar 

  26. Loffet, A. 2002. Peptides as drugs: Is there a market? J Pept Sci 8, 1–7.

    Article  PubMed  CAS  Google Scholar 

  27. Marcus, J.P., Goulter, K.C., Green, J.L., Harrison, S.J., Manners, J.M. 1997. Purification, characterisation and cDNA cloning of an antimicrobial peptide from Macadamia integrifolia. Eur J Biochem 244, 743–749.

    Article  PubMed  CAS  Google Scholar 

  28. McManus, A.M., Nielsen, K.J., Marcus, J.P., Harrison, S.J., Green, J.L., Manners, J.M., Craik, D.J. 1999. MiAMP1, a novel protein from Macadamia integrifolia adopts a Greek key beta-barrel fold unique amongst plant antimicrobial proteins. J Mol Biol 293, 629–638.

    Article  PubMed  CAS  Google Scholar 

  29. Moll, A., Hildebrandt, A., Lenhof, H. P., Kohlbacher, O. 2005. BALLView: An object-oriented molecular visualization and modeling framework. J Comput Aided Mol Des 11, 791–800.

    Article  Google Scholar 

  30. Moll, A., Hildebrandt, A., Lenhof, H.P., Kohlbacher, O. 2006. BALLView: A tool for research and education in molecular modeling. Bioinformatics 22, 365–366.

    Article  PubMed  CAS  Google Scholar 

  31. Mor, A. 2000. Peptide-based antibiotics: A potential answer to raging antimicrobial resistance. Drug Dev Res 50, 440–447.

    Article  CAS  Google Scholar 

  32. Nishio, M., Hirota, M., Umezawa, Y. 1998. The CH/π Interaction. Wiley-VCH, New York.

    Google Scholar 

  33. Pace, C.N., Shirley, B.A., McNutt, M., Gajiwala, K. 1996. Forces contributing to the conformational stability of proteins. FASEB J 10, 75–83.

    PubMed  CAS  Google Scholar 

  34. Ramanathan, K., Sethumadhavan, R., 2009. Exploring the role of C-H…π interactions on the structural stability of antimicrobial peptides. J Theor Comput Chem 8, 909–924.

    Article  CAS  Google Scholar 

  35. Ramanathan, K., Shanthi, V., Sethumadhavan, R. 2009. Contribution of unconventional C-H…O bonds to the structural stability of antimicrobial peptides. Interdiscip Sci Comput Life Sci 1, 263–271.

    Article  CAS  Google Scholar 

  36. Sawa, T., Kurahashi, K., Ohara, M. 1998. Evaluation of antimicrobial and lipopolysaccharide-neutralizing effects of a synthetic CAP18 fragment against Pseudomonas aeruginosa in a mouse model. Antimicrob Agents Chemother 42, 3269–3275.

    PubMed  CAS  Google Scholar 

  37. Stephens, C., Kazan, K., Goulter, K.C., Maclean, D.J., Manners, J.M. 2005. The mode of action of the plant antimicrobial peptide MiAMP1 differs from that of its structural homologue, the yeast killer toxin WmKT. FEMS Microbiol Lett 243, 205–210.

    Article  PubMed  CAS  Google Scholar 

  38. Tiwari, A., Panigrahi, S.K. 2007. HBAT: A complete package for analyzing strong and weak hydrogen bonds in macro molecular crystal structures. In Silico Biol 7, 0057.

    Google Scholar 

  39. Tonks, A. 1994. Drug resistance is a worldwide threat, warns report. BMJ 309, 1109–1110.

    Google Scholar 

  40. Travis, S.M., Anderson, N.N., Forsyth, W.R. 2000. Bactericidal activity of mammalian cathelicidin-derived peptides. Infect Immun 68, 2748–2755.

    Article  PubMed  CAS  Google Scholar 

  41. Vriend, G. 1990. WHAT IF: A molecular modeling and drug design program. J Mol Graph 8, 52–56.

    Article  PubMed  CAS  Google Scholar 

  42. Wahl, M.C., Sundaralingam, M. 1997. C-H…O hydrogen bonding in biology. Trends Biochem Sci 22, 97–102.

    Article  PubMed  CAS  Google Scholar 

  43. 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 

  44. Zanetti, M., Gennaro, R., Romeo, D. 1995. Cathelicidins: A novel protein family with a common proregion and a variabe C-terminal antimicrobial domain. FEBS Lett 374, 1–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India

    K. Ramanathan & Rao Sethumadhavan

Authors
  1. K. Ramanathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rao Sethumadhavan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rao Sethumadhavan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramanathan, K., Sethumadhavan, R. Identifying therapeutic template by evaluating the structural stability of gram positive anti-bacterial peptides-a computational approach. Interdiscip Sci Comput Life Sci 3, 182–188 (2011). https://doi.org/10.1007/s12539-011-0088-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12539-011-0088-3

Key words

Search

Navigation