Skip to main content

POODLE: Tools Predicting Intrinsically Disordered Regions of Amino Acid Sequence

  • Protocol
  • First Online:
Protein Structure Prediction

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1137))

Abstract

Protein intrinsic disorder, a widespread phenomenon characterized by a lack of stable three-dimensional structure, is thought to play an important role in protein function. In the last decade, dozens of computational methods for predicting intrinsic disorder from amino acid sequences have been developed. They are widely used by structural biologists not only for analyzing the biological function of intrinsic disorder but also for finding flexible regions that possibly hinder successful crystallization of the full-length protein. In this chapter, I introduce Prediction Of Order and Disorder by machine LEarning (POODLE), which is a series of programs accurately predicting intrinsic disorder. After giving the theoretical background for predicting intrinsic disorder, I give a detailed guide to using POODLE. I then also briefly introduce a case study where using POODLE for functional analyses of protein disorder led to a novel biological findings.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Institutional subscriptions

References

  1. Wright PE, Dyson HJ (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J Mol Biol 293: 321–331

    Article  CAS  PubMed  Google Scholar 

  2. Dunker AK, Brown CJ, Lawson JD et al (2002) Intrinsic disorder and protein function. Biochemistry 41:6573–6582

    Article  CAS  PubMed  Google Scholar 

  3. Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27:527–533

    Article  CAS  PubMed  Google Scholar 

  4. Uversky VN (2002) Natively unfolded proteins: a point where biology waits for physics. Protein Sci 11:739–756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Tompa P (2005) The interplay between structure and function in intrinsically unstructured proteins. FEBS Lett 579:3346–3354

    Article  CAS  PubMed  Google Scholar 

  6. He B, Wang K, Liu Y et al (2009) Predicting intrinsic disorder in proteins: an overview. Cell Res 19:929–949

    Article  CAS  PubMed  Google Scholar 

  7. Deng X, Eickholt J, Cheng J (2012) A comprehensive overview of computational protein disorder prediction methods. Mol Biosyst 8:114–121

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Longhi S, Receveur-Brechot V, Karlin D et al (2003) The C-terminal domain of the measles virus nucleoprotein is intrinsically disordered and folds upon binding to the C-terminal moiety of the phosphoprotein. J Biol Chem 278:18638–18648

    Article  CAS  PubMed  Google Scholar 

  9. Spinola-Amilibia M, Rivera J, Ortiz-Lombardia M et al (2011) The structure of BRMS1 nuclear export signal and SNX6 interacting region reveals a hexamer formed by antiparallel coiled coils. J Mol Biol 411:1114–1127

    Article  CAS  PubMed  Google Scholar 

  10. Reingewertz TH, Shalev DE, Sukenik S et al (2011) Mechanism of the interaction between the intrinsically disordered C-terminus of the pro-apoptotic ARTS protein and the Bir3 domain of XIAP. PLoS One 6:e24655

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Mcdonald CB, Balke JE, Bhat V et al (2012) Multivalent binding and facilitated diffusion account for the formation of the Grb2-Sos1 signaling complex in a cooperative manner. Biochemistry 51:2122–2135

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Mcdonald CB, Bhat V, Mikles DC et al (2012) Bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner. FEBS J 279:2156–2173

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Khan H, Cino EA, Brickenden A et al (2013) Fuzzy complex formation between the intrinsically disordered prothymosin alpha and the Kelch domain of Keap1 involved in the oxidative stress response. J Mol Biol 425(6): 1011–1027

    Article  CAS  PubMed  Google Scholar 

  14. Ward JJ, Sodhi JS, Mcguffin LJ et al (2004) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J Mol Biol 337:635–645

    Article  CAS  PubMed  Google Scholar 

  15. Motono C, Nakata J, Koike R et al (2011) SAHG, a comprehensive database of predicted structures of all human proteins. Nucleic Acids Res 39:D487–D493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Linding R, Russell RB, Neduva V et al (2003) GlobPlot: exploring protein sequences for globularity and disorder. Nucleic Acids Res 31:3701–3708

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Dunker AK, Obradovic Z, Romero P et al (2000) Intrinsic protein disorder in complete genomes. Genome Inform Ser Workshop Genome Inform 11:161–171

    CAS  PubMed  Google Scholar 

  18. Shimizu K, Muraoka Y, Hirose S et al (2007) Predicting mostly disordered proteins by using structure-unknown protein data. BMC Bioinforma 8:78

    Article  Google Scholar 

  19. Dunker AK, Silman I, Uversky VN et al (2008) Function and structure of inherently disordered proteins. Curr Opin Struct Biol 18: 756–764

    Article  CAS  PubMed  Google Scholar 

  20. Minezaki Y, Homma K, Kinjo AR et al (2006) Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. J Mol Biol 359:1137–1149

    Article  CAS  PubMed  Google Scholar 

  21. Dunker AK, Cortese MS, Romero P et al (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J 272:5129–5148

    Article  CAS  PubMed  Google Scholar 

  22. Dosztanyi Z, Chen J, Dunker AK et al (2006) Disorder and sequence repeats in hub proteins and their implications for network evolution. J Proteome Res 5:2985–2995

    Article  CAS  PubMed  Google Scholar 

  23. Haynes C, Oldfield CJ, Ji F et al (2006) Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes. PLoS Comput Biol 2:e100

    Article  PubMed Central  PubMed  Google Scholar 

  24. Singh GP, Ganapathi M, Dash D (2007) Role of intrinsic disorder in transient interactions of hub proteins. Proteins 66:761–765

    Article  CAS  PubMed  Google Scholar 

  25. Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41:415–427

    Article  CAS  PubMed  Google Scholar 

  26. Linding R, Jensen LJ, Diella F et al (2003) Protein disorder prediction: implications for structural proteomics. Structure 11:1453–1459

    Article  CAS  PubMed  Google Scholar 

  27. Jones DT, Ward JJ (2003) Prediction of disordered regions in proteins from position specific score matrices. Proteins 53(Suppl 6):573–578

    Article  CAS  PubMed  Google Scholar 

  28. Prilusky J, Felder CE, Zeev-Ben-Mordehai T et al (2005) FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics 21:3435–3438

    Article  CAS  PubMed  Google Scholar 

  29. Dosztanyi Z, Csizmok V, Tompa P et al (2005) The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins. J Mol Biol 347:827–839

    Article  CAS  PubMed  Google Scholar 

  30. Shimizu K, Hirose S, Noguchi T (2007) POODLE-S: web application for predicting protein disorder by using physicochemical features and reduced amino acid set of a position-specific scoring matrix. Bioinformatics 23: 2337–2338

    Article  CAS  PubMed  Google Scholar 

  31. Hirose S, Shimizu K, Kanai S et al (2007) POODLE-L: a two-level SVM prediction system for reliably predicting long disordered regions. Bioinformatics 23:2046–2053

    Article  CAS  PubMed  Google Scholar 

  32. Shimizu K, Muraoka Y, Hirose S et al (2005) Feature selection based on physicochemical properties of redefined N-term region and C-term regions for predicting disorder. In: Proceedings of 2005 IEEE symposium on computational intelligence in bioinformatics and computational biology, pp 262–267

    Google Scholar 

  33. Peng K, Radivojac P, Vucetic S et al (2006) Length-dependent prediction of protein intrinsic disorder. BMC Bioinforma 7:208

    Article  Google Scholar 

  34. Ward JJ, Mcguffin LJ, Bryson K et al (2004) The DISOPRED server for the prediction of protein disorder. Bioinformatics 20:2138–2139

    Article  CAS  PubMed  Google Scholar 

  35. Dosztanyi Z, Csizmok V, Tompa P et al (2005) IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21:3433–3434

    Article  CAS  PubMed  Google Scholar 

  36. Yang ZR, Thomson R, Mcneil P et al (2005) RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinformatics 21:3369–3376

    Article  CAS  PubMed  Google Scholar 

  37. Ishida T, Kinoshita K (2007) PrDOS: prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res 35: W460–W464

    Article  PubMed Central  PubMed  Google Scholar 

  38. Hirose S, Shimizu K, Noguchi T (2010) POODLE-I: disordered region prediction by integrating POODLE series and structural information predictors based on a workflow approach. In Silico Biol 10:185–191

    PubMed  Google Scholar 

  39. Xue B, Dunbrack RL, Williams RW et al (2010) PONDR-FIT: a meta-predictor of intrinsically disordered amino acids. Biochim Biophys Acta 1804:996–1010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Ishida T, Kinoshita K (2008) Prediction of disordered regions in proteins based on the meta approach. Bioinformatics 24:1344–1348

    Article  CAS  PubMed  Google Scholar 

  41. Kozlowski LP, Bujnicki JM (2012) MetaDisorder: a meta-server for the prediction of intrinsic disorder in proteins. BMC Bioinforma 13:111

    Article  Google Scholar 

  42. Bordoli L, Kiefer F, Schwede T (2007) Assessment of disorder predictions in CASP7. Proteins

    Google Scholar 

  43. Noivirt-Brik O, Prilusky J, Sussman JL (2009) Assessment of disorder predictions in CASP8. Proteins 77(Suppl 9):210–216

    Article  CAS  PubMed  Google Scholar 

  44. Monastyrskyy B, Fidelis K, Moult J et al (2011) Evaluation of disorder predictions in CASP9. Proteins 79(Suppl 10):107–118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Sakharkar MK, Sakharkar KR, Chow VT (2009) Human genomic diversity, viral genomics and proteomics, as exemplified by human papillomaviruses and H5N1 influenza viruses. Hum Genomics 3:320–331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Scotti C, Olivieri C, Boeri L et al (2011) Bioinformatic analysis of pathogenic missense mutations of activin receptor like kinase 1 ectodomain. PLoS One 6:e26431

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Morita M, Saito S, Ikeda K et al (2009) Structural bases of GM1 gangliosidosis and Morquio B disease. J Hum Genet 54: 510–515

    Article  CAS  PubMed  Google Scholar 

  48. Mcguffin LJ, Bryson K, Jones DT (2000) The PSIPRED protein structure prediction server. Bioinformatics 16:404–405

    Article  CAS  PubMed  Google Scholar 

  49. Cuff JA, Barton GJ (2000) Application of multiple sequence alignment profiles to improve protein secondary structure prediction. Proteins 40:502–511

    Article  CAS  PubMed  Google Scholar 

  50. Adamczak R, Porollo A, Meller J (2005) Combining prediction of secondary structure and solvent accessibility in proteins. Proteins 59:467–475

    Article  PubMed  Google Scholar 

  51. Lupas A, Van Dyke M, Stock J (1991) Predicting coiled coils from protein sequences. Science 252:1162–1164

    Article  CAS  PubMed  Google Scholar 

  52. Soding J, Biegert A, Lupas AN (2005) The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res 33:W244–W248

    Article  PubMed Central  PubMed  Google Scholar 

  53. Shimizu K, Toh H (2009) Interaction between intrinsically disordered proteins frequently occurs in a human protein-protein interaction network. J Mol Biol 392(5):1253–1265

    Article  CAS  PubMed  Google Scholar 

  54. Das S, Mukhopadhyay D (2011) Intrinsically unstructured proteins and neurodegenerative diseases: conformational promiscuity at its best. IUBMB Life 63:478–488

    Article  CAS  PubMed  Google Scholar 

  55. Manich G, Mercader C, Del Valle J et al (2011) Characterization of amyloid-beta granules in the hippocampus of SAMP8 mice. J Alzheimers Dis 25:535–546

    CAS  PubMed  Google Scholar 

  56. Khan SH, Ahmad F, Ahmad N et al (2011) Protein-protein interactions: principles, techniques, and their potential role in new drug development. J Biomol Struct Dyn 28: 929–938

    Article  CAS  PubMed  Google Scholar 

  57. Wang J, Cao Z, Zhao L et al (2011) Novel strategies for drug discovery based on intrinsically disordered proteins (IDPs). Int J Mol Sci 12:3205–3219

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Liu J, Li S, Dunker AK et al (2012) Molecular profiling: an essential technology enabling personalized medicine in breast cancer. Curr Drug Targets 13:541–554

    Article  CAS  PubMed  Google Scholar 

  59. Patil A, Kinoshita K, Nakamura H (2010) Hub promiscuity in protein-protein interaction networks. Int J Mol Sci 11:1930–1943

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Nilsson J, Grahn M, Wright AP (2011) Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins. Genome Biol 12:R65

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Nido GS, Mendez R, Pascual-Garcia A et al (2012) Protein disorder in the centrosome correlates with complexity in cell types number. Mol Biosyst 8:353–367

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

I thank the co-developers of the POODLE series: Dr. Shuichi Hirose, Dr. Satoru Kanai, Dr. Yoichi Muraoka, and Dr. Tamotsu Noguchi. I also thank Dr. Kentaro Tomii, and Dr. Hiroyuki Toh for fruitful discussions.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Shimizu, K. (2014). POODLE: Tools Predicting Intrinsically Disordered Regions of Amino Acid Sequence. In: Kihara, D. (eds) Protein Structure Prediction. Methods in Molecular Biology, vol 1137. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0366-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0366-5_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0365-8

  • Online ISBN: 978-1-4939-0366-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics