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List of disorder prediction software

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Computational methods exploit the sequence signatures of disorder to predict whether a protein is disordered, given its amino acid sequence. The table below, which was originally adapted from[1] and has been recently updated, shows the main features of software for disorder prediction. Note that different software use different definitions of disorder.


Predictor What is predicted Based on Generates and uses multiple sequence alignment?
SLIDER[2] A binary prediction of whether a protein has a long disordered region (>30 residues) Physicochemical properties of amino acids, sequence complexity, and amino acid composition No
SPINE-D[3] Output long/short disorder and semi-disorder (0.4-0.7) and full disorder (0.7-1.0). Semi-disorder is semi-collapsed with some secondary structure. A neural network based three-state predictor based on both local and global features. Ranked in Top 5 based on AUC in CASP 9. Yes
PONDR All regions that are not rigid including random coils, partially unstructured regions, and molten globules Local aa composition, flexibility, hydropathy, etc. No
GlobPlot Regions with high propensity for globularity on the Russell/Linding scale (propensities for secondary structures and random coils) Russell/Linding scale of disorder No
DisEMBL LOOPS (regions devoid of regular secondary structure); HOT LOOPS (highly mobile loops); REMARK465 (regions lacking electron density in crystal structure) Neural networks trained on X-ray structure data No
s2D Predict secondary structure and intrinsic disorder in one unified statistical framework based on the analysis of NMR chemical shifts[4] Neural networks trained on NMR solution-based data. Yes
SEG Low-complexity segments that is, “simple sequences” or “compositionally biased regions”. Locally optimized low-complexity segments are produced at defined levels of stringency and then refined according to the equations of Wootton and Federhen No
Disopred2[5] Regions devoid of ordered regular secondary structure Cascaded support vector machine classifiers trained on PSI-BLAST profiles Yes
FoldIndex[6] Regions that have a low hydrophobicity and high net charge (either loops or unstructured regions) Charge/hydrophaty analyzed locally using a sliding window No
IUPred Regions that lack a well-defined 3D-structure under native conditions Energy resulting from inter-residue interactions, estimated from local amino acid composition No
RONN Regions that lack a well-defined 3D structure under native conditions Bio-basis function neural network trained on disordered proteins No
GeneSilico Metadisorder[7] Regions that lack a well-defined 3D structure under native conditions (REMARK-465) Meta method, which uses other disorder predictors (like RONN, IUPred, POODLE, and many more). Based on them the consensus is calculated according method accuracy (optimized using ANN, filtering and other techniques). Currently the best available method (first 2 places in last CASP experiment (blind test)) Yes
MFDp [8] Different types of disorder including random coils, unstructured regions, molten globules, and REMARK-465-based regions. An ensemble of 3 SVMs specialized for the prediction of short, long and generic disordered regions, which combines three complementary disorder predictors, sequence, sequence profiles, predicted secondary structure, solvent accessibility, backbone dihedral torsion angles, residue flexibility and B-factors. MFDp (unofficially) secured 3rd place in last CASP experiment) Yes
DisPredict_v1.0 [9] Assigns binary order/disorder class and corresponding confidence score for each protein residues using optimized SVM with Radial basis kernel from protein sequence AA composition, Physical Properties, Helix, strand and coil probability, Accessible surface area, torsion angle fluctuation, monogram, bigram. No
MFDp2 [10] Helix, strand and coil probability, relative entropy and per residue disorder prediction. A combination of MFDp and DisCon predictors with unique post processing. Improved prediction over MFDp. Yes
ESpritz Disorder definitions include: missing x-ray atoms (short), Disprot style disorder (long), and NMR flexibility. A probability of disorder is supplied with two decision thresholds which depend on a user preferred false positive rate. Bi-directional neural networks with diverse and high quality data derived from the Protein Data Bank and DisProt. Compares extremely well with other CASP 9 servers. The method was designed to be very fast. No
CSpritz Disorder definitions include: missing x-ray atoms (short) and DisProt style disorder (long). A probability of disorder is supplied with two decision thresholds which depend on the false positive rate. Linear motifs within a disorder segment are determined by simple pattern matching from ELM. Support Vector Machine and Bi-directional neural networks with high quality and diverse data derived from the Protein Data Bank and Disprot. Structural information is also supplied in the form of homologous templates. Compares extremely well with other CASP 9 servers. Yes

Methods not available anymore:

Predictor What is predicted Based on Generates and uses multiple sequence alignment?
OnD-CRF[11] The transition between structurally ordered and mobile or disordered amino acids intervals under native conditions. OnD-CRF applies Conditional Random Fields, CRFs, which rely on features generated from the amino acid sequence and from secondary structure prediction. No
NORSp Regions with No Ordered Regular Secondary Structure (NORS). Most, but not all, are highly flexible. Secondary structure and solvent accessibility Yes
HCA (Hydrophobic Cluster Analysis) Hydrophobic clusters, which tend to form secondary structure elements Helical visualization of amino acid sequence No
PreLink Regions that are expected to be unstructured in all conditions, regardless of the presence of a binding partner Compositional bias and low hydrophobic cluster content. No
MD (Meta-Disorder predictor)[12] Regions of different "types"; for example, unstructured loops and regions containing few stable intra-chain contacts A neural-network based meta-predictor that uses different sources of information predominantly obtained from orthogonal approaches Yes
IUPforest-L Long disordered regions in a set of proteins Moreau-Broto auto-correlation function of amino acid indices (AAIs) No
MeDor (Metaserver of Disorder)[13] Regions of different "types". MeDor provides a unified view of multiple disorder predictors. Meta method, which uses other disorder predictors (like FoldIndex, DisEMBL REMARK465, IUPred, RONN ...) and provides additional features (like HCA plot, Secondary Structure prediction, Transmembrane domains ... ) that all together help the user in defining regions involved in disorder. No


References

  1. ^ Ferron F, Longhi S, Canard B, Karlin D (October 2006). "A practical overview of protein disorder prediction methods". Proteins. 65 (1): 1–14. doi:10.1002/prot.21075. PMID 16856179.
  2. ^ Peng Z, Mizianty MJ, Kurgan L (Jan 2014). "Genome-scale prediction of proteins with long intrinsically disordered regions". Proteins. 82 (1): 145–58. doi:10.1002/prot.24348. PMID 23798504.
  3. ^ Zhang T, Faraggi E, Xue B, Dunker K, Uversky VN, Zhou Y (February 2012). "SPINE-D: Accurate prediction of short and long disordered regions by a single neural-network based method" (PDF). Journal of Biomolecular Structure and Dynamics. 29 (4): 799–813. doi:10.1080/073911012010525022. PMC 3297974. PMID 22208280.
  4. ^ Sormanni P, Camilloni C, Fariselli P, Vendruscolo M (February 2015). "The s2D Method: Simultaneous Sequence- Based Prediction of the Statistical Populations of Ordered and Disordered Regions in Proteins". J. Mol. Biol. 427 (4): 982–996. doi:10.1016/j.jmb.2014.12.007. PMID 25534081.
  5. ^ Ward JJ, Sodhi JS, McGuffin LJ, Buxton BF, Jones DT (March 2004). "Prediction and functional analysis of native disorder in proteins from the three kingdoms of life". J. Mol. Biol. 337 (3): 635–45. doi:10.1016/j.jmb.2004.02.002. PMID 15019783.
  6. ^ Prilusky J, Felder CE, Zeev-Ben-Mordehai T, et al. (August 2005). "FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded". Bioinformatics. 21 (16): 3435–8. doi:10.1093/bioinformatics/bti537. PMID 15955783.
  7. ^ Kozlowski, L. P.; Bujnicki, J. M. (2012). "MetaDisorder: A meta-server for the prediction of intrinsic disorder in proteins". BMC Bioinformatics. 13: 111. doi:10.1186/1471-2105-13-111. PMC 3465245. PMID 22624656.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Mizianty MJ, Stach W, Chen K, Kedarisetti KD, Disfani FM, Kurgan L (September 2010). "Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources". Bioinformatics. 26 (18): i489–96. doi:10.1093/bioinformatics/btq373. PMC 2935446. PMID 20823312.
  9. ^ Sumaiya Iqbal; Md Tamjidul Hoque (October 2015). "DisPredict: A Predictor of Disordered Protein using Optimized RBF Kernel, content and profiles". PLoS One. 10 (10): e0141551. doi:10.1371/journal.pone.0141551.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ Marcin J. Miziantya, Zhenling Penga & Lukasz Kurgan (April 2013). "Accurate predictor of disorder in proteins by fusion of disorder probabilities, content and profiles". Intrinsically Disordered Proteins. 1 (1): e24428. doi:10.4161/idp.24428.
  11. ^ Wang L, Sauer UH (June 2008). "OnD-CRF: predicting order and disorder in proteins using conditional random fields". Bioinformatics. 24 (11): 1401–2. doi:10.1093/bioinformatics/btn132. PMC 2387219. PMID 18430742.
  12. ^ Schlessinger A, Punta M, Yachdav G, Kajan L, Rost B (2009). Orgel, Joseph P. R.14 O. (ed.). "Improved disorder prediction by combination of orthogonal approaches". PLoS ONE. 4 (2): e4433. doi:10.1371/journal.pone.0004433. PMC 2635965. PMID 19209228.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: editors list (link) CS1 maint: unflagged free DOI (link)
  13. ^ Lieutaud P, Canard B, Longhi S (September 2008). "MeDor: a metaserver for predicting protein disorder". BMC Genomics. 16: S25. doi:10.1186/1471-2164-9-S2-S25. PMC 2559890. PMID 18831791.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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