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New PDB Depositions vs. Their Blind AlphaFold Predictions — A Running Test of “Is Folding Solved?”

Release week 2023-03-15

96
structures analysed (10 full · 10.4%)
44.2%
confidently wrong
55.2%
novel sequences
44.2%
novel & wrong
0.921
median TM-score

Zoomed into the red "confidently wrong" box above (pLDDT ≥ 70, TM < 0.5) — the structures AlphaFold got confidently wrong.

The worst offenders ranked, one row per protein (AlphaFold has one model per sequence, so repeat depositions are collapsed — “×N” marks how many structures of that protein exist; the worst is shown). Each row joins what AlphaFold claimed (blue, pLDDT/100) to what the experiment showed (red, TM-score) — the longer the bar, the bigger the miss. Hover a dot to preview its Cα-deviation ribbon; click to open the full entry.

How to read this

Every point is one experimental protein structure. The horizontal axis is AlphaFold's own confidence in its prediction (mean pLDDT, 0–100). The vertical axis is how well that blind prediction actually matches the experiment (TM-score, 0–1; above 0.5 means the same fold, above 0.9 near-identical). Marker size grows with the FRAUD score (confidence-weighted error).

Cutoff: the shaded red box is the "confidently wrong" zone — AlphaFold was confident (mean pLDDT above 70) yet the fold is wrong (TM-score below 0.5). A predictor that had truly solved folding would leave that box empty.

Take-home: 4 of 96 structures (4.2%) are confidently wrong; median TM-score is 0.921.

Read moreShow less — how each metric is calculated

TM-score: how similar the two 3D shapes are overall, 0–1 (a random pair scores ~0.17, an identical fold ~1). Length-normalised so large and small proteins compare fairly. TM = (1/L) Σᵢ 1/(1 + (dᵢ/d₀)²) — dᵢ is the gap between the i-th aligned Cα atoms after best-fit superposition, and d₀ = 1.24(L−15)^⅓ − 1.8 sets the distance scale for length L. Ref: Zhang & Skolnick, Proteins 2004 doi:10.1002/prot.20264; computed with TM-align, doi:10.1093/nar/gki524.

pLDDT: AlphaFold's own confidence in each residue, 0–100 (higher = surer). It is the model predicting its own accuracy before ever seeing the experiment. We plot the per-structure mean. pLDDT = (1/N) Σᵢ pLDDTᵢ, where pLDDTᵢ is the network's confidence output for residue i.

FRAUD score: the headline number — how wrong the prediction was, weighted by how confident AlphaFold was, so a big error it was sure about counts most. FRAUD = (1/N) Σᵢ (pLDDTᵢ/100) · min(Δᵢ,15)/15, where Δᵢ is residue i's Cα distance from the experiment (Å) after superposition, capped at 15 Å. Runs 0 (perfect) to 1.

Novelty: how little AlphaFold had to go on — 100 minus the highest sequence identity between this protein and any structure released before the 2018-04-30 training cutoff. High = genuinely unseen (100% = nothing similar was ever in the training set). novelty = 100 − maxₚ identity(s, p) over pre-cutoff PDB chains p, with identity = 100 × (matching aligned residues)/(alignment length), from an MMseqs2 search.

Homology: the point colour. High novelty (above 70%) flags the sequence as novel (amber) — AlphaFold had no close template; otherwise a pre-cutoff homolog existed (blue) it could have learned the fold from. novel ⇔ novelty > 70%.

What the metrics mean

TM-score (0–1): overall fold match — above 0.5 is the same fold, above 0.9 near-identical. Cα-RMSD (Å): average backbone distance after best-fit superposition — lower is better (under 2 Å is excellent). lDDT (0–1): local accuracy measured without superposition — above 0.8 is good. Each bar counts how many structures fall in that range.

Take-home: median TM-score 0.921 — most predictions match the experimental fold well, with a long tail that do not.

Read moreShow less — how each metric is calculated

TM-score: overall shape match, 0–1 (above 0.5 = same fold, above 0.9 near-identical), length-normalised. TM = (1/L) Σᵢ 1/(1 + (dᵢ/d₀)²) with dᵢ the aligned-Cα gap after superposition and d₀ = 1.24(L−15)^⅓ − 1.8. Ref: Zhang & Skolnick, Proteins 2004 doi:10.1002/prot.20264.

Cα-RMSD: the average straight-line distance between matching backbone Cα atoms once the two structures are best-fit superposed (Å; lower is better, under ~2 Å excellent). RMSD = √( (1/N) Σᵢ |Pᵢ − (R·Qᵢ + t)|² ), with Pᵢ/Qᵢ the experimental/model Cα coordinates and R,t the rotation and translation from Kabsch superposition.

lDDT: local accuracy with no superposition — the fraction of short-range inter-residue distances the model reproduces, so it is not fooled by a single wrongly-placed domain. lDDT = (1/N) Σᵢ ¼ Σ_t 1[ |d_exp − d_model| < t ] over thresholds t ∈ {0.5, 1, 2, 4} Å and all residue pairs within 15 Å.

Trend over time

The blue line is the mean TM-score of the structures by their deposit month; the red bars count how many were confidently wrong. Binning by deposit date (rather than by when we processed them) gives an even timeline, tracking whether AlphaFold's accuracy on newly-deposited structures is holding steady, improving, or slipping as the PDB keeps growing. Months with fewer than 5 structures are omitted so each point is a meaningful average. A dashed trend line is drawn only if the change over time is statistically significant.

Read moreShow less — how each metric is calculated

Mean TM-score: the month's average shape-match score. TM̄ = (1/M) Σ TM over the M structures deposited that month.

Trend line: a monotonic-trend test over the monthly means — Mann-Kendall (Kendall's τ) for significance, with a robust Theil-Sen slope for the line. Rank-based, so it tolerates the skewed TM distribution and noisy low-count months. Shown only when p < 0.05; otherwise a note reports that no significant trend was found.

Confidently wrong: the count that were both confident and wrong. count( mean pLDDT > 70 AND TM < 0.5 ).

Matched structures

PDBUniProtProteinMethodÅDeposited Novelty %pLDDTTMlDDTGDT_TSRMSDFRAUDFlag
7YCX_A Q8N201 Integrator complex subunit 1 EM 4.18 2022-07-02 100.00 novel 81.47 0.45 0.77 0.17 56.49 0.80 wrong
8EQB_C Q9P287 Isoform 2 of BRCA2 and CDKN1A-interacting EM 6.50 2022-10-07 100.00 novel 88.81 0.32 0.30 4.72 19.70 0.73 wrong
8EXF_B Q9P287 BCCIPa X-ray 3.22 2022-10-25 100.00 novel 88.83 0.32 0.30 4.84 19.88 0.73 wrong
8EXE_B Q9P287 Isoform 2 of BRCA2 and CDKN1A-interacting X-ray 3.50 2022-10-25 100.00 novel 88.89 0.31 0.30 4.19 19.93 0.73 wrong
7YCX_H Q75QN2 Integrator complex subunit 8 EM 4.18 2022-07-02 100.00 novel 85.26 0.62 0.87 0.29 12.52 0.68 ok
7YCX_j O00267 Transcription elongation factor SPT5 EM 4.18 2022-07-02 0.00 89.58 0.61 0.84 10.01 14.37 0.59 ok
7U4P_A P05067 Amyloid-beta 17-36 peptide X-ray 1.80 2022-02-28 10.60 49.90 0.34 0.37 11.90 10.61 0.32 ok
7YCX_P P30153 Serine/threonine-protein phosphatase 2A 65 EM 4.18 2022-07-02 94.94 0.77 0.22 ok
7YCX_h P18615 Negative elongation factor E EM 4.18 2022-07-02 0.00 83.03 0.67 0.66 46.59 4.09 0.19 ok
7YCX_K Q5TA45 Integrator complex subunit 11 EM 4.18 2022-07-02 90.69 0.79 0.19 ok
8GSG_B P01308 Insulin B chain X-ray 2.05 2022-09-06 0.00 48.25 0.30 0.46 26.67 6.52 0.18 ok
8ID9_A P63096 Guanine nucleotide-binding protein G(i) su EM 3.00 2023-02-12 93.75 0.81 0.18 ok
7YCX_D Q96HW7 Integrator complex subunit 4 EM 4.18 2022-07-02 83.19 0.79 0.18 ok
8ID4_A P63096 Guanine nucleotide-binding protein G(i) su EM 3.10 2023-02-12 93.75 0.82 0.17 ok
8ID3_A P63096 Guanine nucleotide-binding protein G(i) su EM 3.10 2023-02-12 93.75 0.83 0.16 ok
8ID8_A P63096 Guanine nucleotide-binding protein G(i) su EM 3.00 2023-02-12 93.75 0.83 0.16 ok
8ID6_A P63096 Guanine nucleotide-binding protein G(i) su EM 2.80 2023-02-12 93.75 0.83 0.16 ok
8HJ0_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.12 2022-11-22 89.56 0.83 0.15 ok
8GSG_A P01308 Insulin A chain X-ray 2.05 2022-09-06 0.00 51.25 0.28 0.48 41.67 5.03 0.15 ok
8HJ2_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.80 2022-11-22 89.56 0.85 0.14 ok
8HJ2_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.80 2022-11-22 91.31 0.85 0.13 ok
8HIX_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.12 2022-11-22 91.31 0.86 0.13 ok
8HJ0_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.12 2022-11-22 91.31 0.86 0.13 ok
7YCX_B Q9H0H0 Integrator complex subunit 2 EM 4.18 2022-07-02 78.56 0.84 0.12 ok
7YCX_f Q8WX92 Negative elongation factor B EM 4.18 2022-07-02 84.69 0.87 0.11 ok
7YCX_G Q9NVH2 Integrator complex subunit 7 EM 4.18 2022-07-02 88.06 0.88 0.11 ok
7YCX_I Q9NV88 Integrator complex subunit 9 EM 4.18 2022-07-02 90.94 0.89 0.10 ok
8HIX_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.12 2022-11-22 89.56 0.88 0.10 ok
8EXF_A Q96IP4 Terminal nucleotidyltransferase 5A X-ray 3.22 2022-10-25 79.56 0.87 0.10 ok
8FDG_A P12259 Coagulation factor V EM 3.20 2022-12-03 61.91 0.84 0.10 ok
8EQB_B Q5VWP2 Terminal nucleotidyltransferase 5C EM 6.50 2022-10-07 87.25 0.89 0.10 ok
7UW4_B Q15596 Nuclear receptor coactivator 2 X-ray 2.10 2022-05-02 47.59 0.81 0.09 ok
8ID9_Y P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2023-02-12 89.56 0.90 0.09 ok
7UW2_B Q15596 Nuclear receptor coactivator 2 X-ray 1.88 2022-05-02 47.59 0.82 0.09 ok
8ID8_R Q5NUL3 Free fatty acid receptor 4 EM 3.00 2023-02-12 79.31 0.89 0.09 ok
7YCX_F Q9UL03 Integrator complex subunit 6 EM 4.18 2022-07-02 72.50 0.88 0.08 ok
8A1F_A Q15262 Receptor-type tyrosine-protein phosphatase X-ray 3.00 2022-06-01 82.25 0.90 0.08 ok
8ID3_R Q5NUL3 Free fatty acid receptor 4 EM 3.10 2023-02-12 79.31 0.90 0.08 ok
7YCX_g Q8IXH7 Negative elongation factor C/D EM 4.18 2022-07-02 86.12 0.90 0.08 ok
8ID4_R Q5NUL3 Free fatty acid receptor 4 EM 3.10 2023-02-12 79.31 0.90 0.08 ok
8ID6_R Q5NUL3 Free fatty acid receptor 4 EM 2.80 2023-02-12 79.31 0.90 0.08 ok
8EXE_A Q96IP4 Terminal nucleotidyltransferase 5A X-ray 3.50 2022-10-25 79.56 0.90 0.08 ok
8ID9_R Q5NUL3 Free fatty acid receptor 4 EM 3.00 2023-02-12 79.31 0.90 0.08 ok
7Y4A_B Q92556 Engulfment and cell motility protein 1 X-ray 1.60 2022-06-14 88.88 0.91 0.08 ok
8ID3_Y P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2023-02-12 89.56 0.92 0.07 ok
8I5F_C P60953 Cell division control protein 42 homolog X-ray 2.80 2023-01-25 93.50 0.92 0.07 ok
8ID8_Y P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2023-02-12 89.56 0.92 0.07 ok
7YCX_e Q9H3P2 Negative elongation factor A EM 4.18 2022-07-02 68.50 0.90 0.07 ok
7YCX_E Q6P9B9 Integrator complex subunit 5 EM 4.18 2022-07-02 77.12 0.92 0.06 ok
7XLB_A Q96RD6 Pannexin-2 EM 3.44 2022-04-21 57.19 0.89 0.06 ok
8I5W_B P63000 Ras-related C3 botulinum toxin substrate 1 X-ray 2.43 2023-01-26 93.81 0.94 0.06 ok
8I5V_B P63000 Ras-related C3 botulinum toxin substrate 1 X-ray 1.73 2023-01-26 93.81 0.94 0.05 ok
8C17_A Q15561 Transcriptional enhancer factor TEF-3 X-ray 2.25 2022-12-20 75.19 0.93 0.05 ok
7UAG_A P11413 Glucose-6-phosphate 1-dehydrogenase EM 3.50 2022-03-12 94.38 0.95 0.05 ok
8EQZ_A O75469 Nuclear receptor subfamily 1 group I membe X-ray 2.37 2022-10-11 85.50 0.94 0.05 ok
8ID4_Y P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2023-02-12 89.56 0.95 0.05 ok
8A17_A P28827 Receptor-type tyrosine-protein phosphatase X-ray 3.09 2022-05-31 83.94 0.94 0.05 ok
8A16_A P28827 Receptor-type tyrosine-protein phosphatase X-ray 2.89 2022-05-31 83.94 0.95 0.05 ok
8ID6_Y P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.80 2023-02-12 89.56 0.95 0.04 ok
8CTG_C O75581 Low-density lipoprotein receptor-related p EM 3.80 2022-05-14 79.19 0.95 0.04 ok
7YCX_i P63272 Transcription elongation factor SPT4 EM 4.18 2022-07-02 96.50 0.96 0.04 ok
7XLM_A P50443 Sulfate transporter EM 3.73 2022-04-22 80.88 0.96 0.03 ok
8HIX_R Q99679 Probable G-protein coupled receptor 21 EM 3.12 2022-11-22 83.12 0.96 0.03 ok
8HJ0_R Q99679 Probable G-protein coupled receptor 21 EM 3.12 2022-11-22 83.12 0.96 0.03 ok
8HJ2_R Q99679 Probable G-protein coupled receptor 21 EM 3.80 2022-11-22 83.12 0.96 0.03 ok
7YCX_1 P24928 DNA-directed RNA polymerase II subunit RPB EM 4.18 2022-07-02 76.00 0.96 0.03 ok
8HJ2_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.80 2022-11-22 97.06 0.98 0.02 ok
7X9D_B Q9UJW3 DNA (cytosine-5)-methyltransferase 3-like X-ray 3.08 2022-03-15 86.44 0.98 0.02 ok
7UAH_A P00747 Plasminogen X-ray 1.57 2022-03-12 82.81 0.98 0.02 ok
7U4Q_A P21579 Synaptotagmin-1 X-ray 1.56 2022-02-28 81.81 0.98 0.02 ok
8CXJ_A P13688 Carcinoembryonic antigen-related cell adhe X-ray 3.05 2022-05-21 81.56 0.98 0.01 ok
8E3N_A O75469 Nuclear receptor subfamily 1 group I membe X-ray 2.25 2022-08-17 85.50 0.99 0.01 ok
7YCX_Q P67775 Serine/threonine-protein phosphatase 2A ca EM 4.18 2022-07-02 95.06 0.99 0.01 ok
8FPE_A O75469 Nuclear receptor subfamily 1 group I membe X-ray 2.30 2023-01-04 85.50 0.99 0.01 ok
7Y4A_A P84095 Rho-related GTP-binding protein RhoG X-ray 1.60 2022-06-14 93.94 0.99 0.01 ok
8HJ0_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.12 2022-11-22 97.06 0.99 0.01 ok
7YGY_A Q96C19 EF-hand domain-containing protein D2 X-ray 2.60 2022-07-12 73.75 0.99 0.01 ok
7X9D_A Q9UBC3 DNA (cytosine-5)-methyltransferase 3B X-ray 3.08 2022-03-15 72.56 0.99 0.01 ok
8HIX_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.12 2022-11-22 97.06 0.99 0.01 ok
7TXT_S P31645 Sodium-dependent serotonin transporter EM 3.00 2022-02-09 84.69 0.99 0.01 ok
8ID6_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.80 2023-02-12 97.06 0.99 0.01 ok
8ID3_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2023-02-12 97.06 0.99 0.01 ok
8ID9_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2023-02-12 97.06 0.99 0.01 ok
7U5W_A P00918 Carbonic anhydrase 2 X-ray 1.13 2022-03-02 97.38 0.99 0.01 ok
8ID8_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2023-02-12 97.06 0.99 0.01 ok
8ID4_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2023-02-12 97.06 1.00 0.00 ok
7U5X_A P00918 Carbonic anhydrase 2 X-ray 1.04 2022-03-02 97.38 1.00 0.00 ok
7UW4_A P19793 Retinoic acid receptor RXR-alpha X-ray 2.10 2022-05-02 75.38 0.99 0.00 ok
7UW2_A P19793 Retinoic acid receptor RXR-alpha X-ray 1.88 2022-05-02 75.38 0.99 0.00 ok
8CPM_1 P02794 Ferritin heavy chain, N-terminally process EM 1.81 2023-03-03 95.31 1.00 0.00 ok
8CPS_1 P02794 Ferritin heavy chain, N-terminally process EM 1.82 2023-03-03 95.31 1.00 0.00 ok
8CPT_1 P02794 Ferritin heavy chain, N-terminally process EM 1.79 2023-03-03 95.31 1.00 0.00 ok
8CPU_1 P02794 Ferritin heavy chain, N-terminally process EM 1.76 2023-03-03 95.31 1.00 0.00 ok
8CPX_1 P02794 Ferritin heavy chain, N-terminally process EM 1.76 2023-03-03 95.31 1.00 0.00 ok
8CPV_1 P02794 Ferritin heavy chain, N-terminally process EM 1.76 2023-03-03 95.31 1.00 0.00 ok
8CPW_1 P02794 Ferritin heavy chain, N-terminally process EM 1.79 2023-03-03 95.31 1.00 0.00 ok

Click a column header to sort. FRAUD = confidence-weighted error; a structure is flagged confidently wrong when mean pLDDT > 70 yet TM-score < 0.5.