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Mining proteomes for short motifs (possible potential as bioactive peptides)

Mining proteomes for short motifs (possible potential as bioactive peptides). Proteomes Man pathogens food organisms Computation Evolutionary conservation Evolutionary convergence Predicting SLiM -like properties. Short linear motifs SLiMPRED predictor.

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Mining proteomes for short motifs (possible potential as bioactive peptides)

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  1. Mining proteomes for short motifs(possible potential asbioactive peptides) • Proteomes • Man • pathogens • food organisms • Computation • Evolutionary conservation • Evolutionary convergence • Predicting SLiM-like properties

  2. Short linear motifs SLiMPRED predictor Restricted training set to protein-binding motifs including:

  3. Training a short linear motif predictor (SLiMPred) Most motifs lie in disordered regions of proteins Existing predictor ANCHOR predicts protein-binding within disordered regions

  4. SLiMPred (blue) v ANCHOR (red) Alpha-helix Beta-sheet Polyproline-II helix Other

  5. SLIMPred has some predictive ability in ordered regions too Disordered regions Ordered regions

  6. SLiMPred: predicting motif-like regions along a protein Disorder SLIMPred Relative Local Conservation http://bioware.ucd.ie Mooney et al J Mol Biol (2012) 415:193-204

  7. Which kinds of interactions should we use in searching for novel motifs? ALL Yeast 2 hybrid complex

  8. http://bioinfo-casl.ucd.ie/empa/programberlin/2-uncategorised/52http://bioinfo-casl.ucd.ie/empa/programberlin/2-uncategorised/52

  9. Potential workflows to identify novel peptides from proteins • Conservation analysis • SLiMPrints • Convergent evolution analysis • SLiMFinder • Extracellular peptides • PeptideRanker • Intracellular peptides • SLiMPred • ANCHOR • Known structure of protein ligand, candidate peptide sequence • Pepsite(Trabuco et al Nucleic Acids Res. 2012) • Known structure with linear peptide in complex • Predict cyclised peptide mimetic (CYCLOPS virtual library; Duffy et al 2012).

  10. SLiMFinder humanknown versus the new Known true positive motifs are discovered With variations in many protein interaction sets Novel motifs are much sparser, often only discovered once

  11. All the human motif discovery results are available in an online searchable database (search on genes or motifs)bioware.soton.ac.uk/slimdb

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