Home LiteratureArticle Details
PMID: 14691223 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Protein flexibility and intrinsic disorder.

Protein science : a publication of the Protein Society ·Vol. 13 ·No. 1 ·2004-01-00 ·Pages 71-80

Radivojac P, Obradovic Z, Smith DK, Zhu G, Vucetic S, Brown CJ, Lawson JD, Dunker AK

Abstract

Comparisons were made among four categories of protein flexibility: (1) low-B-factor ordered regions, (2) high-B-factor ordered regions, (3) short disordered regions, and (4) long disordered regions. Amino acid compositions of the four categories were found to be significantly different from each other, with high-B-factor ordered and short disordered regions being the most similar pair. The high-B-factor (flexible) ordered regions are characterized by a higher average flexibility index, higher average hydrophilicity, higher average absolute net charge, and higher total charge than disordered regions. The low-B-factor regions are significantly enriched in hydrophobic residues and depleted in the total number of charged residues compared to the other three categories. We examined the predictability of the high-B-factor regions and developed a predictor that discriminates between regions of low and high B-factors. This predictor achieved an accuracy of 70% and a correlation of 0.43 with experimental data, outperforming the 64% accuracy and 0.32 correlation of predictors based solely on flexibility indices. To further clarify the differences between short disordered regions and ordered regions, a predictor of short disordered regions was developed. Its relatively high accuracy of 81% indicates considerable differences between ordered and disordered regions. The distinctive amino acid biases of high-B-factor ordered regions, short disordered regions, and long disordered regions indicate that the sequence determinants for these flexibility categories differ from one another, whereas the significantly-greater-than-chance predictability of these categories from sequence suggest that flexible ordered regions, short disorder, and long disorder are, to a significant degree, encoded at the primary structure level.

MeSH Terms
Amino Acid Sequence Amino Acids/chemistry Confidence Intervals Databases, Factual Evolution, Molecular Hydrophobic and Hydrophilic Interactions Logistic Models Predictive Value of Tests Protein Conformation Protein Folding Protein Structure, Secondary Proteins/chemistry,genetics Reproducibility of Results Sensitivity and Specificity
Chemicals
Amino Acids Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Radivojac Predrag
Center for Information Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Obradovic Zoran
Smith David K
Zhu Guang
Vucetic Slobodan
Brown Celeste J
Lawson J David
Dunker A Keith
References (49)
49 references, click to expand
  1. The molten globule is a third thermodynamical state of protein molecules.
    FEBS Lett. 1994 Mar 14;341(1):15-8 PMID: 8137915
  2. GenBank.
    Nucleic Acids Res. 1999 Jan 1;27(1):12-7 PMID: 9847132
  3. Structural heterogeneity in protein crystals.
    Biochemistry. 1986 Sep 9;25(18):5018-27 PMID: 3768328
  4. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites.
    J Mol Biol. 1999 Dec 17;294(5):1351-62 PMID: 10600390
  5. What does it mean to be natively unfolded?
    Eur J Biochem. 2002 Jan;269(1):2-12 PMID: 11784292
  6. The Protein Data Bank.
    Nucleic Acids Res. 2000 Jan 1;28(1):235-42 PMID: 10592235
  7. Distribution analysis of the variation of B-factors of X-ray crystal structures; temperature and structural variations in lysozyme.
    J Chem Inf Comput Sci. 1997 Nov-Dec;37(6):1171-80 PMID: 9392860
  8. Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.
    J Mol Biol. 1999 Oct 22;293(2):321-31 PMID: 10550212
  9. Detection of breaking points in helices linking separate domains.
    Proteins. 2001 Feb 15;42(3):390-8 PMID: 11151010
  10. Comparison of the dynamics of myoglobin in different crystal forms.
    Biophys J. 1990 Feb;57(2):381-3 PMID: 2180490
  11. Influence of solvent accessibility and intermolecular contacts on atomic mobilities in hemerythrins.
    Proc Natl Acad Sci U S A. 1985 Feb;82(4):1104-7 PMID: 3856249
  12. Improved amino acid flexibility parameters.
    Protein Sci. 2003 May;12(5):1060-72 PMID: 12717028
  13. Protein secondary structure prediction based on position-specific scoring matrices.
    J Mol Biol. 1999 Sep 17;292(2):195-202 PMID: 10493868
  14. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  15. Coupling of folding and binding for unstructured proteins.
    Curr Opin Struct Biol. 2002 Feb;12(1):54-60 PMID: 11839490
  16. Predicting Disordered Regions from Amino Acid Sequence: Common Themes Despite Differing Structural Characterization.
    Genome Inform Ser Workshop Genome Inform. 1998;9:201-213 PMID: 11072336
  17. The conformational mobility of proteins and its functional significance.
    Biochem Soc Trans. 1978;6(6):1123-6 PMID: 217769
  18. The conformation properties of proteins in solution.
    Biol Rev Camb Philos Soc. 1979 Nov;54(4):389-437 PMID: 230863
  19. Intrinsic disorder and protein function.
    Biochemistry. 2002 May 28;41(21):6573-82 PMID: 12022860
  20. Artificial neural network method for predicting protein secondary structure content.
    Comput Chem. 2002 Jun;26(4):347-50 PMID: 12139417
  21. Sequence complexity of disordered protein.
    Proteins. 2001 Jan 1;42(1):38-48 PMID: 11093259
  22. Amino acid substitution matrices from protein blocks.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9 PMID: 1438297
  23. Reliability of atomic displacement parameters in protein crystal structures.
    Acta Crystallogr D Biol Crystallogr. 1999 Feb;55(Pt 2):473-8 PMID: 10089358
  24. The folding type of a protein is relevant to the amino acid composition.
    J Biochem. 1986 Jan;99(1):153-62 PMID: 3957893
  25. Quantification of secondary structure prediction improvement using multiple alignments.
    Protein Eng. 1993 Nov;6(8):849-54 PMID: 8309932
  26. Flexibility plot of proteins.
    Protein Eng. 1989 May;2(7):497-504 PMID: 2748566
  27. Improving sequence alignments for intrinsically disordered proteins.
    Pac Symp Biocomput. 2002;:589-600 PMID: 11928510
  28. Prediction of protein secondary structure content.
    Protein Eng. 1999 Dec;12(12):1041-50 PMID: 10611397
  29. Review: protein secondary structure prediction continues to rise.
    J Struct Biol. 2001 May-Jun;134(2-3):204-18 PMID: 11551180
  30. Dynamics of proteins in crystals: comparison of experiment with simple models.
    Biophys J. 2002 Aug;83(2):723-32 PMID: 12124259
  31. Natively unfolded proteins: a point where biology waits for physics.
    Protein Sci. 2002 Apr;11(4):739-56 PMID: 11910019
  32. Protein distance constraints predicted by neural networks and probability density functions.
    Protein Eng. 1997 Nov;10(11):1241-8 PMID: 9514112
  33. Relationship of protein flexibility to thermostability.
    Protein Eng. 1987 Dec;1(6):477-80 PMID: 3508295
  34. Identification and functions of usefully disordered proteins.
    Adv Protein Chem. 2002;62:25-49 PMID: 12418100
  35. Study of protein dynamics by X-ray diffraction.
    Methods Enzymol. 1986;131:389-433 PMID: 3773767
  36. Correct structure prediction?
    Nature. 1992 Oct 29;359(6398):781 PMID: 1436052
  37. Flavors of protein disorder.
    Proteins. 2003 Sep 1;52(4):573-84 PMID: 12910457
  38. Alignments grow, secondary structure prediction improves.
    Proteins. 2002 Feb 1;46(2):197-205 PMID: 11807948
  39. Protein fold recognition by prediction-based threading.
    J Mol Biol. 1997 Jul 18;270(3):471-80 PMID: 9237912
  40. Predicting intrinsic disorder from amino acid sequence.
    Proteins. 2003;53 Suppl 6:566-72 PMID: 14579347
  41. Accuracy of protein flexibility predictions.
    Proteins. 1994 Jun;19(2):141-9 PMID: 8090708
  42. Prediction of coordination number and relative solvent accessibility in proteins.
    Proteins. 2002 May 1;47(2):142-53 PMID: 11933061
  43. Analysis of compositionally biased regions in sequence databases.
    Methods Enzymol. 1996;266:554-71 PMID: 8743706
  44. Engineering of stable and fast-folding sequences of model proteins.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7195-9 PMID: 8346235
  45. Identification of common molecular subsequences.
    J Mol Biol. 1981 Mar 25;147(1):195-7 PMID: 7265238
  46. Flexibility and packing in proteins.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1274-9 PMID: 11818549
  47. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
    Nucleic Acids Res. 1997 Sep 1;25(17):3389-402 PMID: 9254694
  48. Evolutionary rate heterogeneity in proteins with long disordered regions.
    J Mol Evol. 2002 Jul;55(1):104-10 PMID: 12165847
  49. Accessibility to internal cavities and ligand binding sites monitored by protein crystallographic thermal factors.
    Proteins. 1998 May 1;31(2):201-13 PMID: 9593193
Article Info
Journal
Protein science : a publication of the Protein Society
Abbr.
Protein Sci
ISSN
0961-8368
DOI
10.1110/ps.03128904
Published
2004-01-00
Pages
71-80
Language
English
Region
United States
NLM ID
9211750
PMCID
PMC2286519
Subset
IM
Grants
NLM NIH HHS · R01 LM006916 · United States
NLM NIH HHS · 1R01 LM06916 · United States
External Links
PubMed source DOI: 10.1110/ps.03128904 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2