AlphaFold2 pLDDT vs. DisProt disorderProduct v1.0.0 · preregistered frozen v0.1 registry

Does confidence mean order?

AlphaFold2 assigns a per-residue confidence score, pLDDT, to every structure it predicts. Alderson et al. (2023, PNAS) showed that low pLDDT is a useful, imperfect signal for intrinsic disorder — and that some experimentally disordered regions still receive confident pLDDT because they can conditionally fold. This project runs a fresh, preregistered, independent test of the same underlying idea against real DisProt-curated disorder annotations, joined to real AlphaFold DB predictions — and reports exactly where the relationship holds and where it does not.

Real per-residue data, not decoration: UniProt Q92793 (DisProt DP02004), residues 645–704 — a 60-residue slice of this 2,442-residue protein. Q92793 carries the largest curated-disorder region in this project's sample, and its DisProt-curated disorder annotation begins at residue 674 (marked with a larger node), which this slice runs into. Each segment's jitter amplitude is (100 − that residue's real pLDDT) from data/external/joined_residues.csv: nearly still above pLDDT 80, visibly restless once pLDDT drops into the 20s and 30s entering the disorder region.

Preregistered protocolReal public data, two sources joinedFrozen result registryFailure modes disclosed, not hidden
01

Sample

387 proteins, 228,662 residues

Proteins joined387human DisProt entries with a usable AlphaFold DB prediction
Total residues228,662every residue of every included protein
Curated-disorder residues36,988DisProt "Structural state" / "disorder" regions
Not curated-disorder191,674outside any DisProt disorder region

Read this before any "predicts disorder well" conclusion below

  • One database snapshot (DisProt, human, accessed 2026-08-13), one AlphaFold DB version per accession, 400-of-1,339 fixed-seed sample — not the full human disorder space, not any other organism.
  • This is not a replication of Alderson et al. (2023)'s exact classifier, database combination, or ROC numbers — it is an independent test of the same general relationship on fresh data, compared to that paper only qualitatively.
  • A pLDDT<70 "not confident" label is not the same as "this residue is disordered," and a confident pLDDT is not the same as "this residue is ordered" — both directions of error are reported below with concrete examples, not just aggregate rates.
  • This project does not evaluate AlphaFold3 and does not make any general claim about intrinsically disordered proteins beyond this dataset.

Full limitations: docs/research-report.md.

02

H1 — preregistered

pLDDT is markedly lower inside curated disorder

pLDDT — inside vs. outside curated disorder regions

Per-residue AlphaFold2 pLDDT (0–100). If the two groups were drawn from the same distribution, these two lines would closely overlap.

pLDDT — inside vs. outside curated disorder regionsEmpirical cumulative distribution comparing 3000 residues inside a curated disorder region (dashed line) against 3000 residues outside one (solid line), pLDDT in pLDDT. Full values are in the accessible data table below this chart.0.000.250.500.751.0019.198.9 pLDDT
Outside curated disorder (solid line), n=3,000 Inside curated disorder (dashed line), n=3,000

Downsampled to at most 3,000 values per group (seed 20260813) for this chart only —every statistic reported alongside it is computed on the full joined dataset.

H1 — pLDDT inside vs. outside curated disorderSignificant (Mann–Whitney U)

Read the complete data table for pLDDT, inside vs. outside curated disorder (chart subsample) (values sorted ascending, pLDDT, 0–100)
pLDDT, inside vs. outside curated disorder (chart subsample)
RowOutside curated disorder (3,000)Inside curated disorder (3,000)
120.2319.06
220.9521.56
321.4722.70
421.5822.80
521.5822.92
622.3122.98
722.8123.06
822.8323.17
922.9523.28
1023.2823.62
1123.6723.67
1223.9723.70
1324.3623.75
1424.4423.92
1524.5623.94
1624.6123.95
1724.6423.95
1824.7024.05
1924.7724.05
2024.8124.11
2125.0924.17
2225.3024.27
2325.4724.30
2425.4724.44
2525.6724.47
2625.7324.48
2725.8424.52
2826.0824.52
2926.0924.62
3026.2224.66
3126.3824.77
3226.3824.78
3326.5024.78
3426.6224.84
3526.6924.84
3626.7024.95
3726.7324.95
3826.7824.95
3926.8025.12
4026.8425.19
4127.1625.22
4227.2325.28
4327.2525.34
4427.4425.36
4527.4825.39
4627.5225.39
4727.6225.42
4827.6725.55
4927.6925.59
5027.7325.59
5127.7525.61
5227.7825.64
5327.8325.67
5427.8425.78
5527.8625.80
5627.8925.81
5727.9225.84
5827.9525.86
5928.0025.89
6028.0026.02
6128.0826.03
6228.1226.12
6328.2226.14
6428.2326.17
6528.2326.19
6628.3426.20
6728.3626.22
6828.3926.25
6928.4226.31
7028.4426.31
7128.4426.31
7228.4826.36
7328.5626.38
7428.5626.41
7528.5826.41
7628.5826.42
7728.6426.42
7828.6926.44
7928.8326.44
8028.8426.45
8128.8426.48
8228.8626.58
8328.8926.61
8428.8926.62
8528.9526.77
8628.9526.80
8729.0026.84
8829.0526.86
8929.0826.88
9029.0926.94
9129.1426.94
9229.2226.95
9329.2826.95
9429.3026.95
9529.3126.97
9629.3326.97
9729.3427.02
9829.3627.03
9929.3927.05
10029.4227.06
10129.5027.06
10229.5027.06
10329.5227.08
10429.5227.08
10529.6227.11
10629.7027.14
10729.8627.19
10829.8627.19
10929.9127.23
11029.9127.23
11129.9427.23
11229.9527.28
11330.0327.28
11430.0327.31
11530.0327.38
11630.0627.39
11730.1127.47
11830.1427.55
11930.1427.56
12030.1727.56
12130.1927.59
12230.2027.61
12330.2827.62
12430.2827.66
12530.3627.69
12630.4127.70
12730.5027.75
12830.5327.80
12930.6227.80
13030.6927.81
13130.7527.81
13230.8027.83
13330.8027.84
13430.8927.84
13530.8927.84
13631.0027.84
13731.0227.86
13831.0527.88
13931.0927.88
14031.0927.88
14131.1127.89
14231.1427.91
14331.1427.91
14431.2827.94
14531.3427.95
14631.3927.97
14731.4527.98
14831.4528.00
14931.5028.03
15031.5328.08
15131.5328.08
15231.5328.08
15331.5528.09
15431.5828.11
15531.6128.11
15631.6228.12
15731.6428.14
15831.6428.16
15931.6728.16
16031.6728.17
16131.6928.19
16231.7728.19
16331.8428.19
16431.8628.19
16531.8828.23
16631.9228.33
16731.9428.34
16832.0028.36
16932.0628.38
17032.1228.38
17132.1628.38
17232.1628.38
17332.2228.38
17432.3428.41
17532.3828.42
17632.3828.42
17732.3828.45
17832.4428.45
17932.4428.45
18032.4728.50
18132.4728.50
18232.5328.52
18332.5628.53
18432.5628.53
18532.5928.55
18632.5928.55
18732.5928.56
18832.5928.56
18932.6228.58
19032.6628.59
19132.6928.59
19232.7228.61
19332.7228.62
19432.7828.62
19532.8428.64
19632.8828.64
19732.8828.66
19833.0928.66
19933.1228.66
20033.1628.72
20133.1628.73
20233.1628.78
20333.1928.80
20433.1928.81
20533.1928.81
20633.2228.83
20733.2528.83
20833.2528.84
20933.2828.84
21033.3428.84
21133.3828.84
21233.4128.88
21333.5028.89
21433.5328.91
21533.5328.92
21633.5628.94
21733.6228.95
21833.6628.95
21933.7828.97
22033.8828.98
22133.9129.00
22233.9729.00
22333.9729.02
22434.0329.02
22534.0629.03
22634.0929.03
22734.1229.11
22834.1229.11
22934.1929.12
23034.2229.14
23134.3429.19
23234.3429.19
23334.3829.25
23434.3829.25
23534.4429.28
23634.4729.33
23734.4729.34
23834.5329.36
23934.5629.38
24034.5929.39
24134.5929.39
24234.6629.41
24334.7229.42
24434.7529.42
24534.7529.47
24634.7829.47
24734.8429.47
24834.8429.50
24934.8829.53
25034.9129.56
25134.9429.58
25235.0029.58
25335.0029.59
25435.0029.59
25535.0329.62
25635.0629.62
25735.0629.62
25835.0629.64
25935.0929.66
26035.1629.66
26135.2229.72
26235.2529.73
26335.2829.73
26435.3129.75
26535.3429.75
26635.3829.75
26735.3829.77
26835.3829.77
26935.3829.77
27035.4129.78
27135.4129.78
27235.4129.80
27335.4129.81
27435.4429.81
27535.4429.83
27635.5029.86
27735.5029.86
27835.5329.88
27935.5629.88
28035.6629.89
28135.6929.89
28235.6929.92
28335.7229.92
28435.7229.92
28535.7229.95
28635.7529.95
28735.7829.97
28835.7829.97
28935.8830.00
29035.8830.05
29135.9130.05
29235.9730.09
29335.9730.09
29435.9730.09
29536.1230.11
29636.1630.12
29736.1930.12
29836.1930.14
29936.1930.16
30036.1930.16
30136.2830.17
30236.2830.19
30336.2830.20
30436.3130.20
30536.3130.23
30636.3130.23
30736.3430.27
30836.3830.30
30936.3830.31
31036.4130.33
31136.4730.34
31236.5030.34
31336.5630.34
31436.6230.34
31536.6230.36
31636.6230.38
31736.6630.38
31836.6630.39
31936.6930.39
32036.6930.41
32136.6930.42
32236.7230.47
32336.8130.47
32436.8130.47
32536.8130.48
32636.8130.52
32736.8130.53
32836.9130.53
32937.0030.56
33037.0030.56
33137.0330.56
33237.0330.59
33337.0930.61
33437.1230.62
33537.1630.62
33637.1930.62
33737.1930.64
33837.1930.64
33937.2230.64
34037.2530.64
34137.2530.64
34237.2830.66
34337.3130.67
34437.3130.69
34537.3830.70
34637.3830.72
34737.4130.72
34837.5030.72
34937.5630.73
35037.5630.77
35137.5630.77
35237.5930.77
35337.6230.78
35437.6930.81
35537.6930.81
35637.7230.81
35737.7830.83
35837.8130.83
35937.8130.84
36037.8130.84
36137.8430.86
36237.8430.88
36338.0630.88
36438.0630.89
36538.0930.89
36638.0930.89
36738.1230.91
36838.1630.91
36938.1930.94
37038.2530.95
37138.2830.97
37238.3130.98
37338.3430.98
37438.3831.00
37538.3831.03
37638.3831.03
37738.4131.05
37838.4131.06
37938.4431.06
38038.4731.06
38138.5031.09
38238.5031.11
38338.5331.11
38438.5931.12
38538.5931.16
38638.5931.16
38738.5931.20
38838.6231.22
38938.6231.22
39038.6931.22
39138.6931.23
39238.7531.23
39338.8131.23
39438.8131.23
39538.8131.25
39638.8431.28
39738.8431.30
39838.8831.30
39938.9131.30
40038.9431.30
40138.9731.31
40239.0031.31
40339.0031.34
40439.0031.34
40539.0331.36
40639.0631.36
40739.0931.39
40839.0931.39
40939.2831.41
41039.2831.41
41139.2831.41
41239.3131.42
41339.3131.44
41439.4131.44
41539.4131.45
41639.4731.47
41739.4731.48
41839.5031.48
41939.5031.48
42039.5631.48
42139.5631.52
42239.5931.53
42339.6231.53
42439.6631.56
42539.6631.58
42639.7831.59
42739.8131.59
42839.9131.59
42939.9731.61
43040.0331.64
43140.0931.67
43240.1631.67
43340.1631.69
43440.1631.69
43540.1931.69
43640.2531.69
43740.2531.70
43840.2531.72
43940.3831.73
44040.4431.73
44140.4731.73
44240.4731.75
44340.5031.75
44440.5031.78
44540.5031.78
44640.5331.80
44740.5631.81
44840.5931.83
44940.6231.89
45040.7231.91
45140.7531.91
45240.8131.92
45340.8831.94
45440.9431.95
45541.0031.95
45641.0331.97
45741.0631.97
45841.1231.97
45941.1232.00
46041.1632.00
46141.1932.03
46241.1932.03
46341.2232.03
46441.3432.03
46541.3832.06
46641.4132.06
46741.4132.06
46841.5032.09
46941.5032.09
47041.5332.12
47141.5632.12
47241.5932.12
47341.5932.12
47441.6232.12
47541.6632.16
47641.6632.16
47741.6632.16
47841.6932.16
47941.6932.19
48041.7832.22
48141.8832.22
48241.9432.22
48341.9732.22
48442.0032.25
48542.0332.25
48642.0632.28
48742.1632.28
48842.1932.28
48942.2832.28
49042.3132.28
49142.3132.28
49242.3832.31
49342.3832.31
49442.3832.31
49542.4132.31
49642.4432.34
49742.4432.34
49842.4732.38
49942.6232.38
50042.6632.38
50142.6632.38
50242.6932.38
50342.7832.41
50442.8132.41
50542.8432.41
50642.8832.41
50742.9132.44
50842.9432.44
50942.9432.44
51043.0332.47
51143.0632.47
51243.1232.50
51343.2232.50
51443.2832.50
51543.3432.53
51643.3832.53
51743.4132.56
51843.4132.56
51943.4732.56
52043.4732.56
52143.4732.59
52243.5032.62
52343.5632.62
52443.5932.62
52543.6232.62
52643.7232.66
52743.7832.66
52843.8132.66
52944.0032.66
53044.0932.66
53144.0932.66
53244.1632.66
53344.2832.69
53444.3132.69
53544.3832.69
53644.3832.69
53744.4132.72
53844.4432.75
53944.5032.75
54044.5032.75
54144.5032.75
54244.5932.75
54344.6232.78
54444.6632.81
54544.6932.81
54644.8832.84
54745.0632.84
54845.0632.88
54945.1232.88
55045.1632.88
55145.1632.91
55245.1932.91
55345.1932.91
55445.2532.91
55545.2832.94
55645.3132.94
55745.3432.97
55845.3432.97
55945.4732.97
56045.5933.00
56145.5933.00
56245.6233.00
56345.6633.00
56445.6933.00
56545.6933.03
56645.7233.03
56745.7533.03
56845.9433.03
56946.0333.03
57046.0633.03
57146.1233.03
57246.3133.03
57346.6233.03
57446.6933.03
57546.8433.06
57647.0933.09
57747.0933.09
57847.1633.09
57947.1633.09
58047.1933.09
58147.2533.12
58247.4433.12
58347.4433.12
58447.5033.12
58547.5933.12
58647.9133.12
58747.9133.16
58848.0633.16
58948.0933.16
59048.1633.19
59148.1633.19
59248.3433.19
59348.3833.19
59448.4433.19
59548.5633.22
59648.6233.22
59748.7833.25
59848.9133.25
59948.9733.25
60049.0633.25
60149.0933.25
60249.1933.25
60349.2233.25
60449.3133.25
60549.3433.28
60649.3833.28
60749.4133.28
60849.5333.28
60949.5933.31
61049.6233.31
61149.7233.31
61249.7833.31
61349.8433.34
61449.8433.34
61550.0333.38
61650.1933.38
61750.3133.41
61850.3833.41
61950.4133.44
62050.4433.44
62150.5933.44
62250.5933.44
62350.6633.47
62450.6633.47
62550.8833.47
62650.9433.47
62750.9433.50
62850.9433.53
62950.9733.53
63051.0933.53
63151.0933.53
63251.0933.53
63351.1233.56
63451.1633.56
63551.5633.59
63651.6233.59
63751.8133.59
63851.8133.62
63951.9733.62
64052.1233.62
64152.2233.62
64252.3833.66
64352.4433.66
64452.4433.66
64552.5333.66
64652.6233.66
64752.7833.66
64852.9133.69
64953.0333.72
65053.0333.72
65153.1633.72
65253.1933.72
65353.3433.72
65453.5033.75
65553.8133.75
65653.8833.78
65753.9433.78
65853.9433.81
65954.0033.81
66054.2833.81
66154.2833.88
66254.2833.88
66354.8833.88
66454.9133.88
66554.9433.91
66654.9733.91
66755.1933.91
66855.2233.91
66955.3133.94
67055.5633.97
67155.5933.97
67255.6233.97
67355.7834.00
67455.9434.00
67556.1234.00
67656.2834.00
67756.3434.03
67856.5934.03
67956.6234.03
68056.6234.06
68156.7234.06
68256.7234.06
68356.8834.06
68457.0334.09
68557.0934.09
68657.3834.09
68757.4134.12
68857.4734.12
68957.6634.12
69057.8134.12
69157.9734.12
69258.3434.16
69358.4134.19
69458.5034.22
69558.5634.22
69658.5634.25
69758.6634.25
69858.7234.25
69958.7534.25
70058.9434.25
70159.0034.28
70259.0934.28
70359.1634.28
70459.2234.31
70559.5634.31
70659.6234.34
70759.8834.34
70859.9134.34
70960.1634.34
71060.6634.38
71160.7534.38
71260.8434.41
71361.1634.41
71461.1934.41
71561.4434.41
71661.7534.41
71761.7834.44
71861.8434.44
71962.0934.44
72062.2234.44
72162.6234.47
72262.7234.47
72362.8134.47
72462.8134.47
72562.8134.50
72662.9134.50
72762.9434.53
72863.0034.53
72963.0934.53
73063.1934.56
73163.3434.56
73263.5334.56
73363.5934.59
73463.6234.59
73563.6234.59
73663.6634.59
73763.7234.59
73863.8834.59
73963.9134.62
74063.9434.62
74163.9434.62
74264.0634.66
74364.3834.66
74464.5034.66
74564.8134.66
74664.8134.69
74764.8834.69
74865.0034.72
74965.1934.72
75065.1934.72
75165.2534.72
75265.3134.72
75365.3834.72
75465.3834.72
75565.4434.72
75665.6234.78
75765.8134.81
75865.8834.81
75965.8834.81
76065.9434.81
76165.9434.81
76265.9434.84
76365.9434.84
76466.0634.84
76566.0634.84
76666.2534.84
76766.2534.88
76866.3834.88
76966.4434.91
77066.4434.91
77166.6234.91
77266.6934.91
77366.6934.94
77466.6934.94
77566.7535.00
77666.8135.00
77767.1235.00
77867.1935.00
77967.2535.00
78067.2535.00
78167.2535.03
78267.2535.03
78367.3135.03
78467.3835.06
78567.7535.06
78667.7535.09
78767.8135.09
78867.8835.09
78967.8835.12
79068.0035.16
79168.0635.16
79268.1935.19
79368.3135.22
79468.3135.22
79568.3135.22
79668.4435.22
79768.5035.22
79868.5635.22
79968.5635.25
80068.6235.28
80168.6235.28
80268.8135.28
80368.9435.28
80469.0035.31
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03

H2 — preregistered

A pLDDT<70 classifier: real signal, moderate strength

Positive class: residue is inside a DisProt-curated disorder region. Predicted positive: pLDDT < 70 ("not confident", per Alderson et al.'s own confident/very-confident boundary). Compared only qualitatively to that paper, not numerically replicated — see the sample panel above.

Overall classifier performance n=228,662 residues

23.5% of curated-disorder residues (8,682 of 36,988) nonetheless received a confident pLDDT (≥70) — directionally and roughly magnitude-consistent with Alderson et al.'s own reported ~30% figure for DisProt, despite this project's different sample, ground-truth scope, and classifier.

Explore the threshold yourself

The report above uses a single, preregistered threshold (pLDDT<70 = "not confident"). Drag the slider to see how precision, recall, F1, and MCC — and the underlying true/false positive/negative counts — change at any other threshold from 0 to 100, computed from the same real 228,662-residue dataset.

pLDDT threshold 70, all curated-disorder residues: precision 34.1%, recall 76.5%, F1 0.472, MCC 0.367. 28,306 true positives, 54,760 false positives, 136,914 true negatives, 8,682 false negatives.

Aggregate view — the headline numbers reported elsewhere on this page.

pLDDT — inside vs. outside curated disorder, with your threshold marked

Same empirical cumulative distribution as above, with a vertical marker at the threshold currently selected on the slider.

pLDDT — inside vs. outside curated disorder, with your threshold markedEmpirical cumulative distribution comparing 3000 residues inside a curated disorder region (dashed line) against 3000 residues outside one (solid line), pLDDT in pLDDT. Full values are in the accessible data table below this chart.0.000.250.500.751.0019.198.9 pLDDTthreshold 70
Outside curated disorder (solid line), n=3,000 Inside curated disorder (dashed line), n=3,000

Downsampled to at most 3,000 values per group (seed 20260813) for this chart only —every statistic reported alongside it is computed on the full joined dataset.

Read the reference table (thresholds 50 / 70 / 90) — no interaction required
Classifier performance at three representative thresholds, aggregate and split by the conditional-folding-flag proxy. A non-interactive equivalent of the slider above.
ThresholdGroupPrecisionRecallF1MCCTPFPTNFN
50Aggregate34.2%57.4%0.4280.29821,23040,936150,73815,758
50Conditional-folding-flagged5.7%45.6%0.1010.0962,47740,936150,7382,958
50No conditional flag31.4%59.4%0.4110.30018,75340,936150,73812,800
70 (preregistered)Aggregate34.1%76.5%0.4720.36728,30654,760136,9148,682
70 (preregistered)Conditional-folding-flagged6.3%68.1%0.1160.1423,70254,760136,9141,733
70 (preregistered)No conditional flag31.0%78.0%0.4440.36024,60454,760136,9146,949
90Aggregate24.8%91.3%0.3900.28433,769102,58989,0853,219
90Conditional-folding-flagged4.5%88.1%0.0850.1144,788102,58989,085647
90No conditional flag22.0%91.8%0.3550.27128,981102,58989,0852,572
04

Exploratory breakdown

Where the relationship breaks down

Disorder on a protein WITH a conditional-folding region elsewhere n=197,109 residues

Disorder on a protein with NO conditional-folding region n=223,227 residues

"WITH a conditional-folding region elsewhere" is a protein-level proxy (does this protein have any "disorder to order" annotation anywhere), not a region-level overlap with the classified residue itself — see the limitations in the full report.

Read the complete evidence-code breakdown (16 codes)
Classifier recall by DisProt evidence code (only codes covering at least 200 curated- disorder residues shown, per the preregistered minimum). Precision is not compared across rows because every row shares the same large non-disorder denominator — see the report.
Evidence codeMeaningDisorder residuesRecall
ECO:0006236protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion57835.1%
ECO:0007691cleavage assay evidence used in manual assertion85951.9%
ECO:0005642heteronuclear single quantum coherence spectroscopy evidence used in manual assertion30857.8%
ECO:0006220X-ray crystallography-based structural model with missing residue coordinates used in manual assertion11,81770.2%
ECO:0006204far-UV circular dichroism evidence used in manual assertion4,33775.7%
ECO:0006165nuclear magnetic resonance spectroscopy evidence used in manual assertion7,56377.2%
ECO:0006003electron microscopy evidence used in manual assertion1,02677.9%
ECO:0007689sodium dodecyl sulfate polyacrylamide gel electrophoresis evidence used in manual assertion63186.1%
ECO:0006224cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion5,54786.7%
ECO:0006198proton-based nuclear magnetic resonance evidence used in manual assertion37589.1%
ECO:0006208cryogenic electron microscopy evidence used in manual assertion23889.5%
ECO:0008035author inference based on intrinsic disorder prediction used in manual assertion62989.7%
ECO:0007680chromatography evidence used in manual assertion77697.6%
ECO:0000302author statement used in manual assertion88298.6%
ECO:0001184gel-filtration evidence used in manual assertion22699.6%
ECO:0007064dynamic light scattering assay evidence used in manual assertion38499.7%
Read the complete per-protein breakdown (385 proteins, sorted by false-negative rate — top 40 shown)
Per-protein classifier failure breakdown: how often curated-disorder residues receive a confident pLDDT (false negative) vs. how often non-disorder residues receive a low pLDDT (false positive), by UniProt accession.
UniProtDisProt IDResiduesDisorder residuesFalse-negative rateFalse positivesConditional?
A6NI73DP0281229911100.0%78no
O00308DP0309287041100.0%235no
P01111DP0388218912100.0%15no
P02788DP0061671022100.0%25no
P06239DP0158050936100.0%91no
P08263DP0150622215100.0%2yes
P13674DP0325953410100.0%45no
P16050DP02162662141100.0%2no
P26196DP0382048313100.0%79no
P33763DP015529215100.0%0no
P37268DP0384241713100.0%65no
P49189DP0278349424100.0%0yes
P49257DP0319051010100.0%131yes
P52848DP0325488235100.0%83no
Q10589DP0288518011100.0%43no
Q7KZI7DP0313078816100.0%371yes
Q8IUQ4DP0260828235100.0%31no
Q99958DP0223150111100.0%403no
Q9UN86DP0399148210100.0%272no
Q01094DP0142743710298.0%270yes
Q14691DP031221965198.0%0no
Q07812DP025401923597.1%23yes
O15392DP037191429996.0%0no
P50148DP0323535921695.4%6no
Q7RTP6DP023962,00211093.6%1,160no
S6B291DP0253146622692.0%37no
Q99523DP015518311291.7%159no
P80303DP0342442023191.3%45yes
P04271DP01738922391.3%1no
P23280DP026803081190.9%35no
Q01081DP0145624011590.4%56yes
O60568DP032607382989.7%36yes
P21583DP009172732788.9%114no
Q16611DP025392113588.6%44yes
O14727DP031731,24810486.5%67no
Q96Q11DP028034346385.7%31no
P02647DP0427126710085.0%82yes
Q9H0E2DP037132745383.0%55yes
P15311DP0077558631081.0%1no
O95155DP031161,3022080.0%348no
05

Reading the result

What this does and does not show

H1 — distribution

Supported at the protein level

The pooled-residue median gap is 43.7 points. A paired analysis across 372 proteins still finds a 36.47-point median gap (protein-cluster 95% CI 34.29–40.07), so the direction survives the dependence among residues.

H2 — classifier

Real signal, moderate strength

MCC 0.367, recall 76.5%, precision 34.1%. Exploratory subgroup performance is lower for conditional-folding-flagged proteins and HDX-MS-supported annotations, but this analysis does not identify the cause of those differences.

What this is not

Not a replication, not a verdict on AlphaFold

Different sample, reference labels, and classifier from Alderson et al. (2023); compared to it only qualitatively. No claim about AlphaFold3 or IDPs generally.

06

Scientific method

How this was built, before any result existed

Data

Two real sources, joined

400 fixed-seed-sampled human DisProt entries joined to AlphaFold DB per-residue pLDDT by UniProt accession; 387 survive disclosed exclusions (7 no prediction, 6 fragmented).

Reference labels

Disclosed, narrow scope

Only DisProt "Structural state"/"disorder" regions count as positive; "disorder to order" regions are tracked separately, never folded into the primary label.

Tests

Mann–Whitney + KS + bootstrap + MCC

Two-sided Mann–Whitney U as the primary H1 test, KS as a robustness check, and a 10,000-resample percentile/multinomial bootstrap for every confidence interval — fixed seed, fully reproducible.

Matthews correlation coefficientMCC = (TP·TN − FP·FN) / √((TP+FP)(TP+FN)(TN+FP)(TN+FN))

Reported alongside precision/recall/F1 because it stays interpretable even with a large true-negative pool, unlike F1 alone.

07

Data & citations

Provenance and further reading