The protein non-folding problem

amino acid determinants of intrinsic order and disorder.

R. M. Williams, Z. Obradovi, V. Mathura, Werner Braun, E. C. Garner, J. Young, S. Takayama, C. J. Brown, A. K. Dunker

Research output: Chapter in Book/Report/Conference proceedingChapter

143 Citations (Scopus)

Abstract

To investigate the determinants of protein order and disorder, three primary and one derivative database of intrinsically disordered proteins were compiled. The segments in each primary database were characterized by one of the following: X-ray crystallography, nuclear magnetic resonance (NMR), or circular dichroism (CD). The derivative database was based on homology. The three primary disordered databases have a combined total of 157 proteins or segments of length.30 with 18,010 residues, while the derivative database contains 572 proteins from 32 families with 52,688 putatively disordered residues. For the four disordered databases, the amino acid compositions were compared with those from a database of ordered structure. Relative to the ordered protein, the intrinsically disordered segments in all four databases were significantly depleted in W, C, F, I, Y, V, L and N, significantly enriched in A, R, G, Q, S, P, E and K, and inconsistently different in H, M, T, and D, suggesting that the first set be called order-promoting and the second set disorder-promoting. Also, 265 amino acid properties were ranked by their ability to discriminate order and disorder and then pruned to remove the most highly correlated pairs. The 10 highest-ranking properties after pruning consisted of 2 residue contact scales, 4 hydrophobicity scales, 3 scales associated with.-sheets and one polarity scale. Using these 10 properties for comparisons of the 3 primary databases suggests that disorder in all 3 databases is very similar, but with those characterized by NMR and CD being the most similar, those by CD and X-ray being next, and those by NMR and X-ray being the least similar.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
Pages89-100
Number of pages12
StatePublished - 2001
Externally publishedYes

Fingerprint

Protein Folding
Databases
Amino Acids
Circular Dichroism
Intrinsically Disordered Proteins
Magnetic Resonance Spectroscopy
X-Rays
Proteins
X Ray Crystallography
Hydrophobic and Hydrophilic Interactions

Cite this

Williams, R. M., Obradovi, Z., Mathura, V., Braun, W., Garner, E. C., Young, J., ... Dunker, A. K. (2001). The protein non-folding problem: amino acid determinants of intrinsic order and disorder. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing (pp. 89-100)

The protein non-folding problem : amino acid determinants of intrinsic order and disorder. / Williams, R. M.; Obradovi, Z.; Mathura, V.; Braun, Werner; Garner, E. C.; Young, J.; Takayama, S.; Brown, C. J.; Dunker, A. K.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2001. p. 89-100.

Research output: Chapter in Book/Report/Conference proceedingChapter

Williams, RM, Obradovi, Z, Mathura, V, Braun, W, Garner, EC, Young, J, Takayama, S, Brown, CJ & Dunker, AK 2001, The protein non-folding problem: amino acid determinants of intrinsic order and disorder. in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. pp. 89-100.
Williams RM, Obradovi Z, Mathura V, Braun W, Garner EC, Young J et al. The protein non-folding problem: amino acid determinants of intrinsic order and disorder. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2001. p. 89-100
Williams, R. M. ; Obradovi, Z. ; Mathura, V. ; Braun, Werner ; Garner, E. C. ; Young, J. ; Takayama, S. ; Brown, C. J. ; Dunker, A. K. / The protein non-folding problem : amino acid determinants of intrinsic order and disorder. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2001. pp. 89-100
@inbook{a443835d06c649bfadf35b3f0cb4bab5,
title = "The protein non-folding problem: amino acid determinants of intrinsic order and disorder.",
abstract = "To investigate the determinants of protein order and disorder, three primary and one derivative database of intrinsically disordered proteins were compiled. The segments in each primary database were characterized by one of the following: X-ray crystallography, nuclear magnetic resonance (NMR), or circular dichroism (CD). The derivative database was based on homology. The three primary disordered databases have a combined total of 157 proteins or segments of length.30 with 18,010 residues, while the derivative database contains 572 proteins from 32 families with 52,688 putatively disordered residues. For the four disordered databases, the amino acid compositions were compared with those from a database of ordered structure. Relative to the ordered protein, the intrinsically disordered segments in all four databases were significantly depleted in W, C, F, I, Y, V, L and N, significantly enriched in A, R, G, Q, S, P, E and K, and inconsistently different in H, M, T, and D, suggesting that the first set be called order-promoting and the second set disorder-promoting. Also, 265 amino acid properties were ranked by their ability to discriminate order and disorder and then pruned to remove the most highly correlated pairs. The 10 highest-ranking properties after pruning consisted of 2 residue contact scales, 4 hydrophobicity scales, 3 scales associated with.-sheets and one polarity scale. Using these 10 properties for comparisons of the 3 primary databases suggests that disorder in all 3 databases is very similar, but with those characterized by NMR and CD being the most similar, those by CD and X-ray being next, and those by NMR and X-ray being the least similar.",
author = "Williams, {R. M.} and Z. Obradovi and V. Mathura and Werner Braun and Garner, {E. C.} and J. Young and S. Takayama and Brown, {C. J.} and Dunker, {A. K.}",
year = "2001",
language = "English (US)",
pages = "89--100",
booktitle = "Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing",

}

TY - CHAP

T1 - The protein non-folding problem

T2 - amino acid determinants of intrinsic order and disorder.

AU - Williams, R. M.

AU - Obradovi, Z.

AU - Mathura, V.

AU - Braun, Werner

AU - Garner, E. C.

AU - Young, J.

AU - Takayama, S.

AU - Brown, C. J.

AU - Dunker, A. K.

PY - 2001

Y1 - 2001

N2 - To investigate the determinants of protein order and disorder, three primary and one derivative database of intrinsically disordered proteins were compiled. The segments in each primary database were characterized by one of the following: X-ray crystallography, nuclear magnetic resonance (NMR), or circular dichroism (CD). The derivative database was based on homology. The three primary disordered databases have a combined total of 157 proteins or segments of length.30 with 18,010 residues, while the derivative database contains 572 proteins from 32 families with 52,688 putatively disordered residues. For the four disordered databases, the amino acid compositions were compared with those from a database of ordered structure. Relative to the ordered protein, the intrinsically disordered segments in all four databases were significantly depleted in W, C, F, I, Y, V, L and N, significantly enriched in A, R, G, Q, S, P, E and K, and inconsistently different in H, M, T, and D, suggesting that the first set be called order-promoting and the second set disorder-promoting. Also, 265 amino acid properties were ranked by their ability to discriminate order and disorder and then pruned to remove the most highly correlated pairs. The 10 highest-ranking properties after pruning consisted of 2 residue contact scales, 4 hydrophobicity scales, 3 scales associated with.-sheets and one polarity scale. Using these 10 properties for comparisons of the 3 primary databases suggests that disorder in all 3 databases is very similar, but with those characterized by NMR and CD being the most similar, those by CD and X-ray being next, and those by NMR and X-ray being the least similar.

AB - To investigate the determinants of protein order and disorder, three primary and one derivative database of intrinsically disordered proteins were compiled. The segments in each primary database were characterized by one of the following: X-ray crystallography, nuclear magnetic resonance (NMR), or circular dichroism (CD). The derivative database was based on homology. The three primary disordered databases have a combined total of 157 proteins or segments of length.30 with 18,010 residues, while the derivative database contains 572 proteins from 32 families with 52,688 putatively disordered residues. For the four disordered databases, the amino acid compositions were compared with those from a database of ordered structure. Relative to the ordered protein, the intrinsically disordered segments in all four databases were significantly depleted in W, C, F, I, Y, V, L and N, significantly enriched in A, R, G, Q, S, P, E and K, and inconsistently different in H, M, T, and D, suggesting that the first set be called order-promoting and the second set disorder-promoting. Also, 265 amino acid properties were ranked by their ability to discriminate order and disorder and then pruned to remove the most highly correlated pairs. The 10 highest-ranking properties after pruning consisted of 2 residue contact scales, 4 hydrophobicity scales, 3 scales associated with.-sheets and one polarity scale. Using these 10 properties for comparisons of the 3 primary databases suggests that disorder in all 3 databases is very similar, but with those characterized by NMR and CD being the most similar, those by CD and X-ray being next, and those by NMR and X-ray being the least similar.

UR - http://www.scopus.com/inward/record.url?scp=0035220932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035220932&partnerID=8YFLogxK

M3 - Chapter

SP - 89

EP - 100

BT - Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing

ER -