Protein flexibility and intrinsic disorder.
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.
Radivojac
Predrag
P
Center for Information Science and Technology, Temple University, Philadelphia, PA 19122, USA.
Obradovic
Zoran
Z
Smith
David K
DK
Zhu
Guang
G
Vucetic
Slobodan
S
Brown
Celeste J
CJ
Lawson
J David
JD
Dunker
A Keith
AK
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
D000596:Amino Acids; D011506:Proteins