A Fourier Transformation based Method to Mine Peptide Space for Antimicrobial Activity

BackgroundNaturally occurring antimicrobial peptides are currently being explored as potential candidate peptide drugs. Since antimicrobial peptides are part of the innate immune system of every living organism, it is possible to discover new candidate peptides using the available genomic and proteomic data. High throughput computational techniques could also be used to virtually scan the entire peptide space for discovering out new candidate antimicrobial peptides.ResultWe have identified a unique indexing method based on biologically distinct characteristic features of known antimicrobial peptides. Analysis of the entries in the antimicrobial peptide databases, based on our indexing method, using Fourier transformation technique revealed a distinct peak in their power spectrum. We have developed a method to mine the genomic and proteomic data, for the presence of peptides with potential antimicrobial activity, by looking for this distinct peak. We also used the Euclidean metric to rank the potential antimicrobial peptides activity. We have parallelized our method so that virtually any given protein space could be data mined, in search of antimicrobial peptides.ConclusionThe results show that the Fourier transform based method with the property based coding strategy could be used to scan the peptide space for discovering new potential antimicrobial peptides.

[1]  M. Yan,et al.  A new fourier transform approach for protein coding measure based on the format of the Z curve , 1998, Bioinform..

[2]  W. Forssmann,et al.  Exploiting natural peptide diversity: novel research tools and drug leads. , 2004, Current opinion in biotechnology.

[3]  Michael Cascio,et al.  De Novo Generation of Cationic Antimicrobial Peptides: Influence of Length and Tryptophan Substitution on Antimicrobial Activity , 2005, Antimicrobial Agents and Chemotherapy.

[4]  Alessandro Tossi,et al.  Tuning the biological properties of amphipathic α-helical antimicrobial peptides: Rational use of minimal amino acid substitutions , 2005, Peptides.

[5]  Takaaki Ohtake,et al.  Biology and clinical relevance of naturally occurring antimicrobial peptides. , 2002, The Journal of allergy and clinical immunology.

[6]  I. Cosic.  Macromolecular bioactivity: is it resonant interaction between macromolecules?-theory and applications , 1994, IEEE Transactions on Biomedical Engineering.

[7]  A. Ouellette,et al.  Paneth cell α-defensins: peptide mediators of innate immunity in the small intestine , 2005, Springer Seminars in Immunopathology.

[8]  Zhe Wang,et al.  APD: the Antimicrobial Peptide Database , 2004, Nucleic Acids Res..

[9]  Ernest Arenas,et al.  The antimicrobial peptide rCRAMP is present in the central nervous system of the rat , 2005, Journal of neurochemistry.

[10]  R. Hancock,et al.  The role of cationic antimicrobial peptides in innate host defences. , 2000, Trends in microbiology.

[11]  R. Gallo,et al.  Expression and Secretion of Cathelicidin Antimicrobial Peptides in Murine Mammary Glands and Human Milk , 2005, Pediatric Research.

[12]  B. Ho,et al.  De Novo Design of Potent Antimicrobial Peptides , 2004, Antimicrobial Agents and Chemotherapy.

[13]  Robert E W Hancock,et al.  Rational Design of α-Helical Antimicrobial Peptides with Enhanced Activities and Specificity/Therapeutic Index* , 2005, Journal of Biological Chemistry.

[14]  M. Buschle,et al.  The artificial antimicrobial peptide KLKLLLLLKLK induces predominantly a TH2-type immune response to co-injected antigens. , 2004, Vaccine.

[15]  M. Selsted,et al.  Mammalian defensins in the antimicrobial immune response , 2005, Nature Immunology.

[16]  Robert E W Hancock,et al.  Design of host defence peptides for antimicrobial and immunity enhancing activities. , 2005, Combinatorial chemistry & high throughput screening.

[17]  William R Taylor,et al.  A Fourier analysis of symmetry in protein structure. , 2002, Protein engineering.

[18]  Ettore Novellino,et al.  Design and Synthesis of Melanocortin Peptides with Candidacidal and Anti-TNF-α Properties , 2005 .

[19]  S. Tiwari,et al.  Prediction of probable genes by Fourier analysis of genomic sequences , 1997, Comput. Appl. Biosci..

[20]  Y. Shai,et al.  Conjugation of fatty acids with different lengths modulates the antibacterial and antifungal activity of a cationic biologically inactive peptide. , 2005, The Biochemical journal.

[21]  Alexander M Cole.  Antimicrobial peptide microbicides targeting HIV. , 2005, Protein and peptide letters.

[22]  A. Ouellette,et al.  Paneth cell alpha-defensins: peptide mediators of innate immunity in the small intestine. , 1998, Springer seminars in immunopathology.

[23]  S J Hamodrakas,et al.  Tandemly repeating peptide motifs and their secondary structure in Ceratitis capitata eggshell proteins Ccs36 and Ccs38. , 1991, International journal of biological macromolecules.

[24]  A. Mclachlan,et al.  Analysis of periodic patterns in amino acid sequences: Collagen , 1977, Biopolymers.

[25]  Thomas Abraham,et al.  Isothermal titration calorimetry studies of the binding of a rationally designed analogue of the antimicrobial peptide gramicidin s to phospholipid bilayer membranes. , 2005, Biochemistry.

[26]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[27]  M. Yeaman,et al.  Multidimensional signatures in antimicrobial peptides. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Blondelle,et al.  Molecular mechanisms of membrane perturbation by antimicrobial peptides and the use of biophysical studies in the design of novel peptide antibiotics. , 2005, Combinatorial chemistry & high throughput screening.

[29]  Friedrich Paulsen,et al.  Human beta-defensin 3 mediates tissue remodeling processes in articular cartilage by increasing levels of metalloproteinases and reducing levels of their endogenous inhibitors. , 2005, Arthritis and rheumatism.

[30]  K. Rabe,et al.  The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung. , 2005, Pulmonary pharmacology & therapeutics.

[31]  D Penny,et al.  A discrete Fourier analysis for evolutionary trees. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Yun Duan,et al.  Predicting protein subcellular location using digital signal processing. , 2005, Acta biochimica et biophysica Sinica.

[33]  C. DeLisi,et al.  Hydrophobicity scales and computational techniques for detecting amphipathic structures in proteins. , 1987, Journal of molecular biology.

[34]  K. Brogden.  Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? , 2005, Nature Reviews Microbiology.

[35]  Gajendra P. S. Raghava,et al.  Spectral Repeat Finder (SRF): identification of repetitive sequences using Fourier transformation , 2004, Bioinform..

[36]  Ettore Novellino,et al.  Design and synthesis of melanocortin peptides with candidacidal and anti-TNF-alpha properties. , 2005, Journal of medicinal chemistry.

[37]  Edgardo Moreno,et al.  Antimicrobial activity of myotoxic phospholipases A2 from crotalid snake venoms and synthetic peptide variants derived from their C-terminal region. , 2005, Toxicon : official journal of the International Society on Toxinology.

[38]  V. Nizet,et al.  Antimicrobial peptides and the skin , 2004, Expert opinion on biological therapy.

[39]  Tin Wee Tan,et al.  ANTIMIC: a database of antimicrobial sequences , 2004, Nucleic Acids Res..