Protein flexibility and intrinsic disorder

Predrag Radivojac, Zoran Obradovic, David K. Smith, Guang Zhu, Slobodan Vucetic, Celeste J. Brown, J. David Lawson, A. Keith Dunker

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224 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalProtein Science
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2004

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Keywords

  • Flexibility prediction
  • Intrinsically unstructured
  • Natively unfolded
  • Temperature factor

ASJC Scopus subject areas

  • Biochemistry

Cite this

Radivojac, P., Obradovic, Z., Smith, D. K., Zhu, G., Vucetic, S., Brown, C. J., Lawson, J. D., & Dunker, A. K. (2004). Protein flexibility and intrinsic disorder. Protein Science, 13(1), 71-80. https://doi.org/10.1110/ps.03128904