PDisorder

PDisorder is the program for predicting ordered and disordered regions in protein sequences. Minimum required sequence length is 40.

It is increasingly evident that intrinsically unstructured protein regions play key roles in cell-signaling, regulation and cancer (Iakoucheva et al., J. Mol. Biol. (2002) 323, 573–584), which makes them extremely useful for discovery of anticancer drugs. Requirement of intrinsic structural disorder is shown for many protein functions - see, for instance, Dunker et al., Biochemistry (2002) 41 (21), 6573 -6582.

The figure below shows disorderly region in Calcineurin (reproduced from ORNL Human Genome News (http://www.ornl.gov/TechResources/Human_Genome/publicat/hgn/v12n1/13trinity.html)), see output example below for prediction of its disorder region.

Combination of Neural Network, Linear Discriminant Function and acute Smoothing Procedure is used for recognition of disordered and ordered regions in proteins.
Two sets of significant attributes: one for Neural Network, and another one for Linear Discriminant Function are selected using automatic LDA procedure, as well as approach based on calculations of chances to be in disordered or ordered regions.
Three windowing procedures are used, called left, right and intermediate. For all windows, attributes are calculated over 31 residues.

 

Example of PDisorder output: 


Prediction of disordered regions in proteins. Softberry Inc.
>gi|1352677|sp|P48457|P2B_EMENI Ser/thr protein phosphatase 2B catalytic subunit
Calmodulin-dependent calcineurin A subunit)
                    10        20        30        40      
 Pred_od    ooooooooo    ddd ooooooooooooooooooooooooooooooooo
 AA seq     MEDGTQVSTLERVVKEVQAPALNKPSDDQFWDPEEPTKPNLQFLKQHFYR
 Prob_o     66666665655663335777766565589767999999999999997999
                    60        70        80        90      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     EGRLTEDQALWIIQAGTQILKSEPNLLEMDAPITVCGDVHGQYYDLMKLF
 Prob_o     99999999999999999999999999999999999999999999999999
                   110       120       130       140      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     EVGGDPAETRYLFLGDYVDRGYFSIECVLYLWALKIWYPNTLWLLRGNHE
 Prob_o     99999999999999999999999999999999999999999999999999
                   160       170       180       190      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     CRHLTDYFTFKLECKHKYSERIYEACIESFCALPLAAVMNKQFLCIHGGL
 Prob_o     99999999999999999999999999999999999997555556887888
                   210       220       230       240      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     SPELHTLEDIKSIDRFREPPTHGLMCDILWADPLEDFGQEKTGDYFIHNS
 Prob_o     78775555553563478776666666678689999999999999999999
                   260       270       280       290      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     VRGCSYFFSYPAACAFLEKNNLLSVIRAHEAQDAGYRMYRKTRTTGFPSV
 Prob_o     99999999999999999999999999999999999999999999999999
                   310       320       330       340      
 Pred_od    oooooooooooooooooooooooooooooooooooooooooooooooooo
 AA seq     MTIFSAPNYLDVYNNKAAVLKYENNVMNIRQFNCTPHPYWLPNFMDVFTW
 Prob_o     99999999999999999999999999999999999999999999999999
                   360       370       380       390      
 Pred_od    ooooooooooo           dddddddddddddddddddddddddddd
 AA seq     SLPFVGEKITDIVIAILNTCSKEELEDETPSTISPAEPSPPMPMDTVDTE
 Prob_o     99999976656555554444441100000000000000000000000000
                   410       420       430       440      
 Pred_od    dddddddddddddddddddddddddddddddddddddddddddddddddd
 AA seq     STEFKRRAIKNKILAIGRLSRVFQVLREESERVTELKTAAGGRLPAGTLM
 Prob_o     00000000000100000000001223333444444333422232555555
                   460       470       480       490      
 Pred_od    dddddddddddddddddddddddddddddddddddddddddddddddddd
 AA seq     LGAEGIKQAITNFEDARKVDLQNERLPPSHDEVVRRSEEERRIALDRAQH
 Prob_o     55555433255544555565443400000231112100000000000001
                   510       520      
 Pred_od    dddddddddddddddddddddddddddddd
 AA seq     EADNDTGLATVARRISMVRRIRKIPSTTRR
 Prob_o     020000022332232444444444443343

sequences=1 disordered=161 ordered=353 unknown=16

Here line Pred_od shows ordered (o) and disordered (d) regions. Blanks denote undefined-state stretches, usually at boundaries of disordered regions.

Line Prob_o shows raw probability on a scale of 0 to 9 for each amino acid residue to be in ordered region.

The line at the end of the output shows total number of sequence residues in each state: disordered, ordered and unknown.

Accuracy estimations:
One of accuracy tests was made on PONDR data and in comparison with PONDR.
Black and blue - PONDR's data, green - our descriptions, red - PDisorder results.

PONDR and PDisorder accuracies

Predictor False Negative (dis_ALL) - 124 sequences >31 in lengths, 17181 positions (false, true) False Positive (O_PDB_S25) - 1081 sequences >31 in lengths, 220743 positions (false, true) 5-cross Validation Unknown
(for both sets)
VL-XT 40% - 22% - 75 - 83% -
XL1 62% - 19% - 73 ± 4% -
CaN 39% - 34% - 83 ± 5% -
PDisorder 20.3% 78.3% 4.7% 94.4% - 0.7%