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

Release week 2022-03-23

114
structures analysed (20 full · 17.5%)
108.8%
confidently wrong
108.8%
novel sequences
108.8%
novel & wrong
0.935
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: 10 of 114 structures (8.8%) are confidently wrong; median TM-score is 0.935.

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 0.935 — 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
7U11_A Q9NUM4 Transmembrane protein 106B EM 3.20 2022-02-19 100.00 novel 94.39 0.17 0.54 0.56 27.20 0.88 wrong
7U18_A Q9NUM4 TMEM106B protein EM 2.70 2022-02-20 100.00 novel 94.39 0.17 0.54 0.56 27.12 0.87 wrong
7U16_A Q9NUM4 Transmembrane protein 106B EM 2.70 2022-02-19 100.00 novel 94.39 0.17 0.54 0.56 27.12 0.87 wrong
7U13_A Q9NUM4 Transmembrane protein 106B EM 2.90 2022-02-19 100.00 novel 94.39 0.17 0.54 0.56 27.14 0.87 wrong
7U10_A Q9NUM4 Transmembrane protein 106B EM 3.00 2022-02-19 100.00 novel 94.39 0.17 0.54 0.56 27.16 0.87 wrong
7U14_A Q9NUM4 Transmembrane protein 106B EM 4.50 2022-02-19 100.00 novel 94.39 0.16 0.54 0.56 27.14 0.87 wrong
7U12_A Q9NUM4 Transmembrane protein 106B EM 3.50 2022-02-19 100.00 novel 94.39 0.18 0.53 0.56 27.07 0.87 wrong
7U17_A Q9NUM4 Transmembrane protein 106B EM 3.00 2022-02-19 100.00 novel 94.39 0.16 0.51 0.93 26.43 0.87 wrong
7U15_A Q9NUM4 Transmembrane protein 106B EM 3.00 2022-02-19 100.00 novel 94.39 0.16 0.51 0.93 26.43 0.87 wrong
7QJX_A P10636 Microtubule-associated protein tau EM 2.99 2021-12-17 0.00 67.87 0.24 0.46 0.00 24.68 0.66 ok
7QKJ_A P10636 Microtubule-associated protein tau EM 3.26 2021-12-17 0.00 67.98 0.25 0.47 1.00 23.63 0.63 ok
7U0Z_A P10636 Isoform Tau-E of Microtubule-associated pr EM 4.20 2022-02-19 0.00 66.23 0.22 0.45 1.36 21.42 0.60 ok
7T3U_A Q14573 Inositol 1,4,5-trisphosphate receptor type EM 3.70 2021-12-08 38.80 80.95 0.68 0.85 8.89 13.76 0.56 ok
7TYH_E O60895 Receptor activity-modifying protein 2 EM 3.30 2022-02-13 0.00 96.49 0.65 0.82 38.14 5.25 0.29 ok
7TYY_E O60895 Receptor activity-modifying protein 2 EM 3.00 2022-02-14 0.00 96.02 0.69 0.89 37.87 5.31 0.29 ok
7P2K_A Q6ZNA4 E3 ubiquitin-protein ligase Arkadia NMR 2021-07-06 1.50 81.85 0.60 0.62 30.43 8.82 0.28 ok
7TYF_E O60894 Receptor activity-modifying protein 1 EM 2.20 2022-02-13 89.75 0.72 0.25 ok
7TZF_E O60896 Receptor activity-modifying protein 3 EM 2.40 2022-02-15 87.56 0.75 0.22 ok
7TYW_E O60894 Receptor activity-modifying protein 1 EM 3.00 2022-02-14 2.20 95.72 0.65 0.80 51.16 3.52 0.20 ok
7WUB_D P55072 Transitional endoplasmic reticulum ATPase EM 3.00 2022-02-08 82.56 0.76 0.19 ok
7WUB_C P55072 Transitional endoplasmic reticulum ATPase EM 3.00 2022-02-08 82.56 0.76 0.19 ok
7WUB_A P55072 Transitional endoplasmic reticulum ATPase EM 3.00 2022-02-08 82.56 0.76 0.19 ok
7VL8_A P63096 Guanine nucleotide-binding protein G(i) su EM 2.90 2021-10-02 93.75 0.82 0.17 ok
7VL9_A P63096 Guanine nucleotide-binding protein G(i) su EM 2.60 2021-10-02 93.75 0.82 0.17 ok
7TYH_P P01258 Calcitonin EM 3.30 2022-02-13 15.70 62.15 0.43 0.72 39.84 4.82 0.16 ok
7VLA_A P63096 Guanine nucleotide-binding protein G(i) su EM 2.70 2021-10-02 93.75 0.83 0.16 ok
7TYO_P P01258 Calcitonin EM 2.70 2022-02-14 15.70 62.15 0.44 0.76 43.75 4.69 0.16 ok
7EEK_A P02768 Serum albumin X-ray 2.50 2021-03-18 92.69 0.84 0.15 ok
7T3T_A Q14573 Inositol 1,4,5-trisphosphate receptor type EM 3.80 2021-12-08 73.44 0.80 0.15 ok
7FB5_B Q9H6L5 Reticulophagy regulator 1 X-ray 2.84 2021-07-08 100.00 novel 72.67 0.34 0.78 51.19 3.28 0.14 wrong
7WKX_E Q16552 Interleukin-17A X-ray 2.81 2022-01-12 84.31 0.83 0.14 ok
7TYL_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.30 2022-02-13 89.56 0.85 0.14 ok
7T3R_A Q14573 Inositol 1,4,5-trisphosphate receptor type EM 3.40 2021-12-08 73.44 0.83 0.13 ok
7TYO_A P63092 Guanine nucleotide-binding protein G(s) su EM 2.70 2022-02-14 91.31 0.86 0.13 ok
7TYF_A P63092 Guanine nucleotide-binding protein G(s) su EM 2.20 2022-02-13 91.31 0.87 0.12 ok
7TYL_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.30 2022-02-13 91.31 0.87 0.12 ok
7TYW_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.00 2022-02-14 91.31 0.87 0.12 ok
7T3Q_A Q14573 Inositol 1,4,5-trisphosphate receptor type EM 3.30 2021-12-08 73.44 0.84 0.12 ok
7TYH_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.30 2022-02-13 91.31 0.87 0.12 ok
7TZF_A P63092 Guanine nucleotide-binding protein G(s) su EM 2.40 2022-02-15 91.31 0.87 0.12 ok
7TYY_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.00 2022-02-14 91.31 0.87 0.12 ok
7NAL_A Q6SZW1 NAD(+) hydrolase SARM1 EM 3.00 2021-06-21 85.69 0.86 0.12 ok
7T3P_A Q14573 Inositol 1,4,5-trisphosphate receptor type EM 3.20 2021-12-08 73.44 0.85 0.11 ok
7TYH_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.30 2022-02-13 89.56 0.89 0.10 ok
7VL9_L Q16663 CCL15(26-92) EM 2.60 2021-10-02 78.00 0.87 0.10 ok
7T4R_A P07204 Thrombomodulin EM 3.30 2021-12-10 78.62 0.88 0.10 ok
7VLA_L Q16663 CCL15(27-92) EM 2.70 2021-10-02 78.00 0.88 0.09 ok
7TYL_R P30988 Calcitonin receptor EM 3.30 2022-02-13 78.69 0.89 0.09 ok
7TZF_R P30988 Calcitonin receptor EM 2.40 2022-02-15 78.69 0.89 0.08 ok
7TYW_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2022-02-14 89.56 0.91 0.08 ok
7TYF_R P30988 Calcitonin receptor EM 2.20 2022-02-13 78.69 0.90 0.08 ok
7TYO_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.70 2022-02-14 89.56 0.91 0.08 ok
7VL8_R P32246 C-C chemokine receptor type 1 EM 2.90 2021-10-02 83.19 0.93 0.06 ok
7VLA_R P32246 C-C chemokine receptor type 1 EM 2.70 2021-10-02 83.19 0.93 0.06 ok
7VL9_R P32246 C-C chemokine receptor type 1 EM 2.60 2021-10-02 83.19 0.93 0.06 ok
7TZF_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.40 2022-02-15 89.56 0.93 0.06 ok
7TYY_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2022-02-14 89.56 0.93 0.06 ok
7TYY_R P30988 Calcitonin receptor EM 3.00 2022-02-14 78.69 0.93 0.06 ok
7N3A_A P22914 Gamma-crystallin S X-ray 1.50 2021-05-31 95.31 0.94 0.06 ok
7TYF_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.20 2022-02-13 89.56 0.95 0.05 ok
7TYH_R P30988 Calcitonin receptor EM 3.30 2022-02-13 78.69 0.94 0.05 ok
7VLA_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.70 2021-10-02 89.56 0.95 0.05 ok
7TYW_R P30988 Calcitonin receptor EM 3.00 2022-02-14 78.69 0.94 0.05 ok
7VL8_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.90 2021-10-02 89.56 0.95 0.05 ok
7N36_A P22914 Gamma-crystallin S X-ray 2.00 2021-05-31 95.31 0.95 0.04 ok
7NAK_A Q6SZW1 NAD(+) hydrolase SARM1 EM 2.90 2021-06-21 85.69 0.95 0.04 ok
7NNJ_A Q9NZJ9 Diphosphoinositol polyphosphate phosphohyd X-ray 1.75 2021-02-24 85.00 0.96 0.04 ok
7N38_A P22914 Gamma-crystallin S X-ray 1.22 2021-05-31 95.31 0.96 0.04 ok
7TYO_R P30988 Calcitonin receptor EM 2.70 2022-02-14 78.69 0.96 0.03 ok
7NAG_A Q6SZW1 Sterile alpha and TIR motif-containing pro X-ray 1.72 2021-06-21 85.69 0.96 0.03 ok
7NAI_A Q6SZW1 Sterile alpha and TIR motif-containing pro X-ray 1.74 2021-06-21 85.69 0.96 0.03 ok
7N37_A P22914 Gamma-crystallin S X-ray 1.30 2021-05-31 95.31 0.97 0.03 ok
7NAJ_A Q6SZW1 Sterile alpha and TIR motif-containing pro X-ray 1.60 2021-06-21 85.69 0.96 0.03 ok
7NAH_A Q6SZW1 Sterile alpha and TIR motif-containing pro X-ray 1.79 2021-06-21 85.69 0.96 0.03 ok
7VL9_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 2.60 2021-10-02 89.56 0.97 0.03 ok
7Z7F_A Q9Y5A9 YTH domain-containing family protein 2 X-ray 1.95 2022-03-15 59.50 0.96 0.03 ok
7L1C_A P04439 HLA class I histocompatibility antigen, A X-ray 1.96 2020-12-14 87.12 0.98 0.02 ok
7L1D_B P61769 Beta-2-microglobulin X-ray 3.11 2020-12-14 94.06 0.98 0.02 ok
7L1B_A P04439 HLA class I histocompatibility antigen, A X-ray 2.04 2020-12-14 87.12 0.98 0.02 ok
7RRG_B P61769 Beta-2-microglobulin X-ray 2.12 2021-08-09 94.06 0.98 0.02 ok
7NR6_A Q9NV35 Probable 8-oxo-dGTP diphosphatase NUDT15 X-ray 1.80 2021-03-03 92.75 0.98 0.02 ok
7L1C_B P61769 Beta-2-microglobulin X-ray 1.96 2020-12-14 94.06 0.98 0.02 ok
7L1D_A P04439 HLA class I histocompatibility antigen, A X-ray 3.11 2020-12-14 87.12 0.98 0.01 ok
7A6T_A P49366 Deoxyhypusine synthase X-ray 1.66 2020-08-26 94.06 0.99 0.01 ok
7FHS_A Q13627 Dual specificity tyrosine-phosphorylation- X-ray 2.42 2021-07-30 66.44 0.98 0.01 ok
7FHT_A Q13627 Dual specificity tyrosine-phosphorylation- X-ray 2.68 2021-07-30 66.44 0.98 0.01 ok
7TYL_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.30 2022-02-13 97.06 0.99 0.01 ok
7R54_A Q9NR97 Toll-like receptor 8 X-ray 2.84 2022-02-10 86.12 0.99 0.01 ok
7N39_A P22914 Gamma-crystallin S X-ray 1.56 2021-05-31 95.31 0.99 0.01 ok
7A6S_A P49366 Deoxyhypusine synthase X-ray 1.75 2020-08-26 94.06 0.99 0.01 ok
7L1B_B P61769 Beta-2-microglobulin X-ray 2.04 2020-12-14 94.06 0.99 0.01 ok
7NPM_AAA P03950 Angiogenin X-ray 1.86 2021-02-27 89.81 0.99 0.01 ok
7R53_A Q9NR97 Toll-like receptor 8 X-ray 3.12 2022-02-10 86.12 0.99 0.01 ok
7RRG_A P04439 HLA class I histocompatibility antigen, A X-ray 2.12 2021-08-09 87.12 0.99 0.01 ok
7TYH_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.30 2022-02-13 97.06 0.99 0.01 ok
7TYY_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2022-02-14 97.06 0.99 0.01 ok
7RWH_A P31153 S-adenosylmethionine synthase isoform type X-ray 1.17 2021-08-19 96.06 0.99 0.01 ok
7RW7_A P31153 S-adenosylmethionine synthase isoform type X-ray 1.19 2021-08-19 96.06 0.99 0.01 ok
7PSU_A P68400 Casein kinase II subunit alpha X-ray 1.77 2021-09-23 88.94 0.99 0.01 ok
7RWG_A P31153 S-adenosylmethionine synthase isoform type X-ray 0.97 2021-08-19 96.06 0.99 0.01 ok
7TYW_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2022-02-14 97.06 0.99 0.01 ok
7N3B_A P22914 Gamma-crystallin S X-ray 2.09 2021-05-31 95.31 0.99 0.01 ok
7R52_A Q9NR97 Toll-like receptor 8 X-ray 2.94 2022-02-10 86.12 0.99 0.01 ok
7RW5_A P31153 S-adenosylmethionine synthase isoform type X-ray 2.48 2021-08-19 96.06 0.99 0.01 ok
7TYO_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.70 2022-02-14 97.06 0.99 0.01 ok
7T4S_F O60462 Neuropilin-2 EM 3.10 2021-12-10 78.62 0.99 0.01 ok
7VXG_A Q06124 Tyrosine-protein phosphatase non-receptor X-ray 2.10 2021-11-12 85.94 0.99 0.00 ok
7TZF_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.40 2022-02-15 97.06 1.00 0.00 ok
7E3M_A P51449 Nuclear receptor ROR-gamma X-ray 2.80 2021-02-09 74.19 0.99 0.00 ok
7VLA_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.70 2021-10-02 97.06 1.00 0.00 ok
7VL8_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.90 2021-10-02 97.06 1.00 0.00 ok
7TYF_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.20 2022-02-13 97.06 1.00 0.00 ok
7VL9_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 2.60 2021-10-02 97.06 1.00 0.00 ok
7NS7_A P21549 L-alanine:glyoxylate aminotransferase X-ray 2.20 2021-03-05 98.31 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.