Prediction of Intrinsic Disorder and Its Use in Functional Proteomics

  • Vladimir N. Uversky
  • Predrag Radivojac
  • Lilia M. Iakoucheva
  • Zoran Obradovic
  • A. Keith Dunker
Part of the Methods in Molecular Biology™ book series (MIMB, volume 408)


The number of experimentally verified, intrinsically disordered (ID) proteins is rapidly rising. Research is often focused on a structural characterization of a given protein, looking for several key features. However, ID proteins with their dynamic structures that interconvert on a number of time-scales are difficult targets for the majority of traditional biophysical and biochemical techniques. Structural and functional analyses of these proteins can be significantly aided by disorder predictions. The current advances in the prediction of ID proteins and the use of protein disorder prediction in the fields of molecular biology and bioinformatics are briefly overviewed herein. A method is provided to utilize intrinsic disorder knowledge to gain structural and functional information related to individual proteins, protein groups, families, classes, and even entire proteomes.

Key Words

Intrinsically disordered protein natively unfolded protein intrinsically unstructured protein protein flexibility disorder prediction protein function 


  1. 1.
    Fischer, E. (1894) Einfluss der configuration auf die wirkung der enzyme. Ber. Dtsch. Chem. Ges. 27, 2985–2993.CrossRefGoogle Scholar
  2. 2.
    Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., Brown, C. J., and Dunker, A. K. (2003) Predicting intrinsic disorder from amino acid sequence. Proteins 53, 566–572.CrossRefPubMedGoogle Scholar
  3. 3.
    Linderstrom-Lang, K. U. and Schellman, J. A. (1959) Protein structure and enzyme activity, in The Enzymes, (Boyer, P. D., Lardy, H., and Myrback, K., eds.), Academic Press, New York, pp. 443–510.Google Scholar
  4. 4.
    Pullen, R. A., Jenkins, J. A., Tickle, I. J., Wood, S. P., and Blundell, T. L. (1975) The relation of polypeptide hormone structure and flexibility to receptor binding: the relevance of X-ray studies on insulins, glucagon and human placental lactogen. Mol. Cell Biochem. 8, 5–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Cary, P. D., Moss, T., and Bradbury, E. M. (1978) High-resolution proton-magneticresonance studies of chromatin core particles. Eur. J. Biochem. 89, 475–482.CrossRefPubMedGoogle Scholar
  6. 6.
    Holt, C. and Sawyer, L. (1993) Caseins as rheomorphic proteins: interpretation of primary and secondary structures of the αs1-, β-, and κ-caseins. J. Chem. Soc. Faraday Trans. 89, 2683–269CrossRefGoogle Scholar
  7. 7.
    Schweers, O., Schoenbrunn-Hanebeck, E., Marx, A., and Mandelkow, E. (1994) Structural studies of tau protein and alzheimer paired helical filaments show no evidence for β-structure. J. Biol. Chem. 269, 24,290–24,297.PubMedGoogle Scholar
  8. 8.
    Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., and Lansbury, P. T., Jr. (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35, 13,709–13,715.CrossRefPubMedGoogle Scholar
  9. 9.
    Wright, P. E. and Dyson, H. J. (1999) Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm. J. Mol. Biol. 293, 321–331.CrossRefPubMedGoogle Scholar
  10. 10.
    Dunker, A. K., Lawson, J. D., Brown, C. J., et al. (2001) Intrinsically disordered protein. J. Mol. Graph. Model 19, 26–59.CrossRefPubMedGoogle Scholar
  11. 11.
    Daughdrill, G. W., Pielak, G. J., Uversky, V. N., Cortese, M. S., and Dunker, A. K. (2005) Natively disordered protein, in Protein Folding Handbook, (Buchner, J. and Kiefhaber, T. eds.), Wiley-VCH: Verlag GmbH & Co., KGaA, Weinheim, pp. 271–353.Google Scholar
  12. 12.
    Uversky, V. N. (2003) A protein-chameleon: conformational plasticity of alphasynuclein, a disordered protein involved in neurodegenerative disorders. J. Biomol. Struct. Dyn. 21, 211–234.PubMedGoogle Scholar
  13. 13.
    Uversky, V. N., Oldfield, C. J., and Dunker, A. K. (2005) Showing your ID: intrinsic disorder as an ID for regcognition, regulation, and cell signaling. J. Mol. Recognit. 18, 343–384.CrossRefPubMedGoogle Scholar
  14. 14.
    Dunker, A. K. and Obradovic, Z. (2001) The protein trinity-linking function and disorder. Nat. Biotechnol. 19, 805, 806.CrossRefPubMedGoogle Scholar
  15. 15.
    Uversky, V. N. (2002) Natively unfolded proteins: a point where biology waits for physics. Protein Sci. 11, 739–756.CrossRefPubMedGoogle Scholar
  16. 16.
    Ringe, D. and Petsko, G. A. (1986) Study of protein dynamics by X-ray diffraction. Methods Enzymol. 131, 389–433.CrossRefPubMedGoogle Scholar
  17. 17.
    Dyson, H. J. and Wright, P. E. (2002) Insights into the structure and dynamics of unfolded proteins from nuclear magnetic resonance. Adv. Protein Chem. 62, 311–340.CrossRefPubMedGoogle Scholar
  18. 18.
    Bracken, C., Iakoucheva, L. M., Romero, P. R., and Dunker, A. K. (2004) Combining prediction, computation and experiment for the characterization of protein disorder. Curr. Opin. Struct. Biol. 14, 570–576.CrossRefPubMedGoogle Scholar
  19. 19.
    Dyson, H. J. and Wright, P. E. (2004) Unfolded proteins and protein folding studied by NMR. Chem. Rev. 104, 3607–3622.CrossRefPubMedGoogle Scholar
  20. 20.
    Dyson, H. J. and Wright, P. E. (2005) Elucidation of the protein folding landscape by NMR. Methods Enzymol. 394, 299–321.CrossRefPubMedGoogle Scholar
  21. 21.
    Fasman, G. D. (1996) Circular dichroism and the conformational analysis of biomolecules. Plenum Press, New York.Google Scholar
  22. 22.
    Adler, A. J., Greenfield, N. J., and Fasman, G. D. (1973) Circular dichroism and optical rotatory dispersion of proteins and polypeptides. Methods Enzymol. 27, 675–735.CrossRefPubMedGoogle Scholar
  23. 23.
    Provencher, S. W. and Glockner, J. (1981) Estimation of globular protein secondary structure from circular dichroism. Biochemistry 20, 33–37.CrossRefPubMedGoogle Scholar
  24. 24.
    Woody, R. W. (1995) Circular dichroism. Methods Enzymol. 246, 34–71.CrossRefPubMedGoogle Scholar
  25. 25.
    Uversky, V. N., Gillespie, J. R., and Fink, A. L. (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41, 415–427.CrossRefPubMedGoogle Scholar
  26. 26.
    Smyth, E., Syme, C. D., Blanch, E. W., Hecht, L., Vasak, M., and Barron, L. D. (2001) Solution structure of native proteins with irregular folds from Raman optical activity. Biopolymers 58, 138–151.CrossRefPubMedGoogle Scholar
  27. 27.
    Uversky, V. N. (1999) A multiparametric approach to studies of self-organization of globular proteins. Biochemistry (Mosc) 64, 250–266.Google Scholar
  28. 28.
    Receveur-Brechot, V., Bourhis, J. M., Uversky, V. N., Canard, B., and Longhi, S. (2006) Assessing protein disorder and induced folding. Proteins 62, 24–45.CrossRefPubMedGoogle Scholar
  29. 29.
    Glatter, O. and Kratky, O. (1982) Small angle X-ray scattering. Academic Press, London.Google Scholar
  30. 30.
    Markus, G. (1965) Protein substrate conformation and proteolysis. Proc. Natl. Acad. Sci. USA 54, 253–258.CrossRefPubMedGoogle Scholar
  31. 31.
    Mikhalyi, E. (1978) Application of proteolytic enzymes to protein structure studies. CRC Press, Boca Raton.Google Scholar
  32. 32.
    Hubbard, S. J., Eisenmenger, F., and Thornton, J. M. (1994) Modeling studies of the change in conformation required for cleavage of limited proteolytic sites. Protein Sci. 3, 757–768.CrossRefPubMedGoogle Scholar
  33. 33.
    Fontana, A., de Laureto, P. P., de Filippis, V., Scaramella, E., and Zambonin, M. (1997) Probing the partly folded states of proteins by limited proteolysis. Fold. Des. 2, R17–R26.CrossRefPubMedGoogle Scholar
  34. 34.
    Fontana, A., de Laureto, P. P., Spolaore, B., Frare, E., Picotti, P., and Zambonin, M. (2004) Probing protein structure by limited proteolysis. Acta Biochim. Pol. 51, 299–321.PubMedGoogle Scholar
  35. 35.
    Iakoucheva, L. M., Kimzey, A. L., Masselon, C. D., Smith, R. D., Dunker, A. K., and Ackerman, E. J. (2001) Aberrant mobility phenomena of the DNA repair protein XPA. Protein Sci. 10, 1353–1362.CrossRefPubMedGoogle Scholar
  36. 36.
    Tompa, P. (2002) Intrinsically unstructured proteins. Trends Biochem. Sci. 27, 527–533.CrossRefPubMedGoogle Scholar
  37. 37.
    Privalov, P. L. (1979) Stability of proteins: small globular proteins. Adv. Protein Chem. 33, 167–241.CrossRefPubMedGoogle Scholar
  38. 38.
    Ptitsyn, O. (1995) Molten globule and protein folding. Adv. Protein Chem. 47, 83–229.CrossRefPubMedGoogle Scholar
  39. 39.
    Ptitsyn, O. B. and Uversky, V. N. (1994) The molten globule is a third thermodynamical state of protein molecules. FEBS Lett. 341, 15–18.CrossRefPubMedGoogle Scholar
  40. 40.
    Uversky, V. N. and Ptitsyn, O. B. (1996) All-or-none solvent-induced transitions between native, molten globule and unfolded states in globular proteins. Fold. Des. 1, 117–122.CrossRefPubMedGoogle Scholar
  41. 41.
    Westhof, E., Altschuh, D., Moras, D., et al. (1984) Correlation between segmental mobility and the location of antigenic determinants in proteins. Nature 311, 123–126.CrossRefPubMedGoogle Scholar
  42. 42.
    Berzofsky, J. A. (1985) Intrinsic and extrinsic factors in protein antigenic structure. Science 229, 932–940.CrossRefPubMedGoogle Scholar
  43. 43.
    Iakoucheva, L. M., Brown, C. J., Lawson, J. D., Obradovic, Z., and Dunker, A. K. (2002) Intrinsic disorder in cell-signaling and cancer-associated proteins. J. Mol. Biol. 323, 573–584.CrossRefPubMedGoogle Scholar
  44. 44.
    Dunker, A. K., Cortese, M. S., Romero, P., Iakoucheva, L. M., and Uversky, V. N. (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 272, 5129–5148.CrossRefPubMedGoogle Scholar
  45. 45.
    Dunker, A. K., Brown, C. J., Lawson, J. D., Iakoucheva, L. M., and Obradovic, Z. (2002) Intrinsic disorder and protein function. Biochemistry 41, 6573–6582.CrossRefPubMedGoogle Scholar
  46. 46.
    Xie, H., Vucetic, S., Iakoucheva, L. M., et al. (2007) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 6, 1882–1898.CrossRefPubMedGoogle Scholar
  47. 47.
    Vucetic, S., Xie, H., Iakoucheva, L. M., et al. (2007) Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J. Proteome Res. 6, 1899–1916.CrossRefPubMedGoogle Scholar
  48. 48.
    Xie, H., Vucetic, S., Iakoucheva, L. M., et al. (2007) Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications and diseases associated with intrinsically disordered proteins. J. Proteome Res. 6, 1917–1932.CrossRefPubMedGoogle Scholar
  49. 49.
    Sim, K. L., Uchida, T., and Miyano, S. (2001) ProDDO: a database of disordered proteins from the Protein Data Bank (PDB). Bioinformatics 17, 379–380.CrossRefPubMedGoogle Scholar
  50. 50.
    Vucetic, S., Obradovic, Z., Vacic, V., et al. (2005) DisProt: a database of protein disorder. Bioinformatics 21, 137–140.CrossRefPubMedGoogle Scholar
  51. 51.
    Romero, P., Obradovic, Z., Li, X., Garner, E. C., Brown, C. J., and Dunker, A. K. (2001) Sequence complexity of disordered protein. Proteins 42, 38–48.CrossRefPubMedGoogle Scholar
  52. 52.
    Wootton, J. C. (1993) Statistic of local complexity in amino acid sequences and sequence databases. Comput. Chem. 17, 149–163.CrossRefGoogle Scholar
  53. 53.
    Radivojac, P., Obradovic, Z., Smith, D. K., et al. (2004) Protein flexibility and intrinsic disorder. Protein Sci. 13, 71–80.CrossRefPubMedGoogle Scholar
  54. 54.
    Romero, P., Obradovic, Z., Kissinger, C. R., Villafranca, J. E., and Dunker, A. K. (1997) Identifying disordered regions in proteins from amino acid sequences. IEEE Int. Conf. Neural Netw. 1, 90–95.Google Scholar
  55. 55.
    Lise, S. and Jones, D. T. (2005) Sequence patterns associated with disordered regions in proteins. Proteins 58, 144–150.CrossRefPubMedGoogle Scholar
  56. 56.
    Li, X., Romero, P., Rani, M., Dunker, A. K., and Obradovic, Z. (1999) Predicting protein disorder for N-, C-, and internal regions. Genome Inform. Ser. Workshop Genome Inform. 10, 30–40.PubMedGoogle Scholar
  57. 57.
    Dunker, A. K., Obradovic, Z., Romero, P., Garner, E. C., and Brown, C. J. (2000) Intrinsic protein disorder in complete genomes. Genome Inform. Ser. Workshop Genome Inform. 11, 161–171.PubMedGoogle Scholar
  58. 58.
    Oldfield, C. J., Cheng, Y., Cortese, M. S., Brown, C. J., Uversky, V. N., and Dunker, A. K. (2005) Comparing and combining predictors of mostly disordered proteins. Biochemistry 44, 1989–2000.CrossRefPubMedGoogle Scholar
  59. 59.
    Vucetic, S., Radivojac, P., Obradovic, Z., Brown, C. J., and Dunker, A. K. (2001) Methods for improving protein disorder prediction, in International Joint INNSIEEE Conference on Neural Networks, Washington, DC, pp. 2718–2723.Google Scholar
  60. 60.
    Vucetic, S., Brown, C. J., Dunker, A. K., and Obradovic, Z. (2003) Flavors of protein disorder. Proteins 52, 573–584.CrossRefPubMedGoogle Scholar
  61. 61.
    Melamud, E. and Moult, J. (2003) Evaluation of disorder predictions in CASP5. Proteins 53(Suppl 6), 561–565.CrossRefPubMedGoogle Scholar
  62. 62.
    Jin, Y. and Dunbrack, R. L., Jr. (2005) Assessment of disorder predictions in CASP6. Proteins 61(Suppl 7), 167–175.CrossRefPubMedGoogle Scholar
  63. 63.
    Jones, D. T. and Ward, J. J. (2003) Prediction of disordered regions in proteins from position specific score matrices. Proteins 53, 573–578.CrossRefPubMedGoogle Scholar
  64. 64.
    Jones, D. T. (1999) Protein secondary structure prediction based on position-specific scoring matrices. J. Mol. Biol. 292, 195–202.CrossRefPubMedGoogle Scholar
  65. 65.
    Peng, K., Vucetic, S., Radivojac, P., Brown, C. J., Dunker, A. K., and Obradovic, Z. (2005) Optimizing long intrinsic disorder predictors with protein evolutionary information. J. Bioinformatics Comput. Biol. 3, 35–60.CrossRefGoogle Scholar
  66. 66.
    Linding, R., Russell, R. B., Neduva, V., and Gibson, T. J. (2003) GlobPlot: exploring protein sequences for globularity and disorder. Nucleic Acids Res. 31, 3701–3708.CrossRefPubMedGoogle Scholar
  67. 67.
    Linding, R., Jensen, L. J., Diella, F., Bork, P., Gibson, T. J., and Russell, R. B. (2003) Protein disorder prediction: implications for structural proteomics. Structure 11, 1453–1459.CrossRefPubMedGoogle Scholar
  68. 68.
    Liu, J., Tan, H., and Rost, B. (2002) Loopy proteins appear conserved in evolution. J. Mol. Biol. 322, 53–64.CrossRefPubMedGoogle Scholar
  69. 69.
    Liu, J. and Rost, B. (2003) NORSp: Predictions of long regions without regular secondary structure. Nucleic Acids Res. 31, 3833–3835.CrossRefPubMedGoogle Scholar
  70. 70.
    Ward, J. J., Sodhi, J. S., McGuffin, L. J., Buxton, B. F., and Jones, D. T. (2004) Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J. Mol. Biol. 337, 635–645.CrossRefPubMedGoogle Scholar
  71. 71.
    Ward, J. J., McGuffin, L. J., Bryson, K., Buxton, B. F., and Jones, D. T. (2004) The DISOPRED server for the prediction of protein disorder. Bioinformatics 20, 2138–2139.CrossRefPubMedGoogle Scholar
  72. 72.
    Dosztanyi, Z., Csizmok, V., Tompa, P., and Simon, I. (2005) The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins. J. Mol. Biol. 347, 827–839.CrossRefPubMedGoogle Scholar
  73. 73.
    Dosztanyi, Z., Csizmok, V., Tompa, P., and Simon, I. (2005) IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21, 3433–3434.CrossRefPubMedGoogle Scholar
  74. 74.
    Prilusky, J., Felder, C. E., 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.CrossRefPubMedGoogle Scholar
  75. 75.
    Yang, Z. R., Thomson, R., McNeil, P., and Esnouf, R. M. (2005) RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinformatics 21, 3369–3376.CrossRefPubMedGoogle Scholar
  76. 76.
    Coeytaux, K. and Poupon, A. (2005) Prediction of unfolded segments in a protein sequence based on amino acid composition. Bioinformatics 21, 1891–1900.CrossRefPubMedGoogle Scholar
  77. 77.
    Cheng, J., Sweredoski, M. J., and Baldi, P. (2005) Accurate prediction of protein disordered regions by mining protein structure data. Data Mining Knowledge Disc. 11, 213–222.CrossRefGoogle Scholar
  78. 78.
    Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., and Dunker, A. K. (2005) Exploiting heterogeneous sequence properties improves prediction of protein disorder. Proteins 61(Suppl 7), 176–182.CrossRefPubMedGoogle Scholar
  79. 79.
    Peng, K., Radivojac, P., Vucetic, S., Dunker, A. K., and Obradovic, Z. (2006) Lengthdependent prediction of protein intrinsic disorder. BMC Bioinformatics 7, 208.CrossRefPubMedGoogle Scholar
  80. 80.
    Vullo, A., Bortolami, O., Pollastri, G., and Tosatto, S. C. (2006) Spritz: a server for the prediction of intrinsically disordered regions in protein sequences using kernel machines. Nucleic Acids Res. 34, W164–W168.CrossRefPubMedGoogle Scholar
  81. 81.
    Garner, E., Romero, P., Dunker, A. K., Brown, C., and Obradovic, Z. (1999) Predicting binding regions within disordered proteins. Genome Inform. Ser. Workshop Genome Inform. 10, 41–50.PubMedGoogle Scholar
  82. 82.
    Oldfield, C. J., Cheng, Y., Cortese, M. S., Romero, P., Uversky, V. N., and Dunker, A. K. (2005) Coupled folding and binding with alpha-helix-forming molecular recognition elements. Biochemistry 44, 12,454–12,470.CrossRefPubMedGoogle Scholar
  83. 83.
    Iakoucheva, L. M., Radivojac, P., Brown, C. J., et al. (2004) The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 32, 1037–1049.CrossRefPubMedGoogle Scholar
  84. 84.
    Ritter, L. M., Arakawa, T., and Goldberg, A. F. (2005) Predicted and measured disorder in peripherin/rds, a retinal tetraspanin. Protein Pept. Lett. 12, 677–686.CrossRefPubMedGoogle Scholar
  85. 85.
    Kukhtina, V., Kottwitz, D., Strauss, H., et al. (2005) Intracellular domain of nicotinic acetylcholine receptor: the importance of being unfolded. J. Neurochem. Google Scholar
  86. 86.
    Yiu, C. P., Beavil, R. L., and Chan, H. Y. (2006) Biophysical characterisation reveals structural disorder in the nucleolar protein, Dribble. Biochem. Biophys. Res. Commun. 343, 311–318.CrossRefPubMedGoogle Scholar
  87. 87.
    Hinds, M. G., Smits, C., Fredericks-Short, R., et al. (2007) Bim, Bad and Bmf: intrinsically unstructured BH3-only proteins that undergo a localized conformational change on binding to prosurvival Bcl-2 targets. Cell Death Differ. 14, 128–136.CrossRefPubMedGoogle Scholar
  88. 88.
    Nardini, M., Svergun, D., Konarev, P. V., et al. (2006) The C-terminal domain of the transcriptional corepressor CtBP is intrinsically unstructured. Protein Sci. 15, 1042–1050.CrossRefPubMedGoogle Scholar
  89. 89.
    Roy, S., Schnell, S., and Radivojac, P. (2007) Unraveling the nature of the segmentation clock: intrinsic disorder of clock proteins and their interaction map. Comput. Biol. Chem. 30, 241–248.CrossRefGoogle Scholar
  90. 90.
    Popovic, M., Coglievina, M., Guarnaccia, C., et al. (2006) Gene synthesis, expression, purification, and characterization of human Jagged-1 intracellular region. Protein Expr. Purif. 47, 398–404.CrossRefPubMedGoogle Scholar
  91. 91.
    Cheng, Y., Le Gall, T., Oldfield, C. J., Dunker, A. K., and Uversky, V. N. (2006) Abundance of intrinsic disorder in proteins associated with cardiovascular disease. Biochemistry 45, 10,448–10,460.CrossRefPubMedGoogle Scholar
  92. 92.
    Liu, J., Perumal, N. B., Oldfield, C. J., Su, E. W., Uversky, V. N., and Dunker, A. K. (2006) Intrinsic disorder in transcription factors. Biochemistry 45, 6873–6888.CrossRefPubMedGoogle Scholar
  93. 93.
    Singh, G. P., Ganapathi, M., Sandhu, K. S., and Dash, D. (2006) Intrinsic unstructuredness and abundance of PEST motifs in eukaryotic proteomes. Proteins 62, 309–315.CrossRefPubMedGoogle Scholar
  94. 94.
    Hansen, J. C., Lu, X., Ross, E. D., and Woody, R. W. (2006) Intrinsic protein disorder, amino acid composition, and histone terminal domains. J. Biol. Chem. 281, 1853–1856.CrossRefPubMedGoogle Scholar
  95. 95.
    Haynes, C. and Iakoucheva, L. M. (2006) Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins. Nucleic Acids Res. 34, 305–312.CrossRefPubMedGoogle Scholar
  96. 96.
    Bustos, D. M. and Iglesias, A. A. (2006) Intrinsic disorder is a key characteristic in partners that bind 14-3-3 proteins. Proteins 63, 35–42.CrossRefPubMedGoogle Scholar
  97. 97.
    Denning, D. P., Patel, S. S., Uversky, V., Fink, A. L., and Rexach, M. (2003) Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc. Natl. Acad. Sci. USA 100, 2450–2455.CrossRefPubMedGoogle Scholar
  98. 98.
    Boeckmann, B., Bairoch, A., Apweiler, R., et al. (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 31, 365–370.CrossRefPubMedGoogle Scholar
  99. 99.
    Daily, K. M., Radivojac, P., and Dunker, A. K. (2005) Intrinsic disorder and protein modifications: building an SVM predictor for methylation, in IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology, CIBCB 2005, San Diego, California, CA, pp.475–481.Google Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Vladimir N. Uversky
    • 1
    • 2
  • Predrag Radivojac
    • 3
  • Lilia M. Iakoucheva
    • 4
  • Zoran Obradovic
    • 5
  • A. Keith Dunker
    • 1
  1. 1.School of MedicineIndiana UniversityIndianapolis
  2. 2.Russian Academy of SciencesMoscow RegionRussia
  3. 3.School of InformaticsIndiana UniversityBloomington
  4. 4.The Rockefeller University New York
  5. 5.Temple UniversityPhiladelphia

Personalised recommendations