title: Protein flexibility and intrinsic disorder.
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.
authors.affiliation: Center for Information Science and Technology, Temple University, Philadelphia, PA 19122, USA.
authors.forename: Predrag
authors.initials: P
authors.lastname: Radivojac
authors.forename: Zoran
authors.initials: Z
authors.lastname: Obradovic
authors.forename: David K
authors.initials: DK
authors.lastname: Smith
authors.forename: Guang
authors.initials: G
authors.lastname: Zhu
authors.forename: Slobodan
authors.initials: S
authors.lastname: Vucetic
authors.forename: Celeste J
authors.initials: CJ
authors.lastname: Brown
authors.forename: J David
authors.initials: JD
authors.lastname: Lawson
authors.forename: A Keith
authors.initials: AK
authors.lastname: Dunker
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D016001:Confidence Intervals; D016208:Databases, Factual; D019143:Evolution, Molecular; D057927:Hydrophobic and Hydrophilic Interactions; D016015:Logistic Models; D011237:Predictive Value of Tests; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000596:Amino Acids; D011506:Proteins