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

Release week 2021-11-03

103
structures analysed (3 full · 2.9%)
11.0%
confidently wrong
00.0%
novel sequences
00.0%
novel & wrong
0.948
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: 1 of 103 structures (1.0%) are confidently wrong; median TM-score is 0.948.

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 0.948 — 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
7DW5_A P0CJ85 Double homeobox protein 4-like protein 2 X-ray 2.83 2021-01-15 0.00 95.60 0.49 0.96 0.00 21.97 0.93 wrong
7DEE_A O15519 CASP8 and FADD-like apoptosis regulator NMR 2020-11-03 78.31 0.77 0.18 ok
7SHN_A P33897 ATP-binding cassette sub-family D member 1 EM 3.10 2021-10-09 80.62 0.82 0.15 ok
7RMG_S P20366 Substance P EM 3.00 2021-07-27 58.73 0.28 0.67 50.00 3.58 0.13 ok
7RMH_S P20366 Substance P EM 3.10 2021-07-27 58.73 0.26 0.70 50.00 3.45 0.13 ok
7F55_A P63092 Isoform Gnas-2 of Guanine nucleotide-bindi EM 3.10 2021-06-21 91.31 0.86 0.12 ok
7F54_A P63092 Isoform Gnas-2 of Guanine nucleotide-bindi EM 3.00 2021-06-21 91.31 0.86 0.12 ok
7RMH_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-07-27 89.56 0.86 0.12 ok
7F53_A P63092 Isoform Gnas-2 of Guanine nucleotide-bindi EM 3.00 2021-06-21 91.31 0.86 0.12 ok
7RMH_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.10 2021-07-27 91.31 0.87 0.12 ok
7RHL_A P29973 cGMP-gated cation channel alpha-1 EM 3.03 2021-07-17 76.25 0.84 0.12 ok
7F58_A P63092 Isoform Gnas-2 of Guanine nucleotide-bindi EM 3.10 2021-06-21 91.31 0.87 0.12 ok
7RMI_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.20 2021-07-27 91.31 0.87 0.11 ok
7RMG_A P63092 Guanine nucleotide-binding protein G(s) su EM 3.00 2021-07-27 91.31 0.88 0.11 ok
7RMI_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.20 2021-07-27 89.56 0.88 0.11 ok
7L4V_A P17676 CCAAT/enhancer-binding protein beta X-ray 1.75 2020-12-21 59.69 0.83 0.10 ok
7EG1_B Q8IYM2 Schlafen family member 12 EM 3.20 2021-03-23 82.81 0.88 0.10 ok
7RHL_B Q14028 Cyclic nucleotide-gated cation channel bet EM 3.03 2021-07-17 57.66 0.86 0.08 ok
7ARX_A P48740 Mannan-binding lectin serine protease 1 X-ray 2.42 2020-10-26 90.44 0.91 0.08 ok
7RHK_A P29973 cGMP-gated cation channel alpha-1 EM 3.27 2021-07-17 76.25 0.90 0.08 ok
7RD5_E O95858 Tetraspanin-15 X-ray 3.60 2021-07-09 87.56 0.91 0.08 ok
7RH9_A P29973 cGMP-gated cation channel alpha-1 EM 2.61 2021-07-16 76.25 0.90 0.08 ok
7RHG_A P29973 cGMP-gated cation channel alpha-1 EM 2.88 2021-07-17 76.25 0.90 0.08 ok
7RHH_B Q14028 Cyclic nucleotide-gated cation channel bet EM 3.31 2021-07-17 57.66 0.87 0.08 ok
7SHM_A P33897 ATP-binding cassette sub-family D member 1 EM 3.14 2021-10-09 80.62 0.91 0.07 ok
7F55_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-06-21 89.56 0.92 0.07 ok
7F54_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-06-21 89.56 0.92 0.07 ok
7F53_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-06-21 89.56 0.92 0.07 ok
7RDB_A O95858 Tetraspanin-15 X-ray 2.52 2021-07-09 87.56 0.92 0.07 ok
7RHJ_A P29973 cGMP-gated cation channel alpha-1 EM 2.88 2021-07-17 76.25 0.91 0.07 ok
7RHH_A P29973 cGMP-gated cation channel alpha-1 EM 3.31 2021-07-17 76.25 0.91 0.07 ok
7RHK_B Q14028 Cyclic nucleotide-gated cation channel bet EM 3.27 2021-07-17 57.66 0.89 0.07 ok
7RHJ_B Q14028 Cyclic nucleotide-gated cation channel bet EM 2.88 2021-07-17 57.66 0.89 0.06 ok
7RMG_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-07-27 89.56 0.93 0.06 ok
7RHI_A P29973 cGMP-gated cation channel alpha-1 EM 3.31 2021-07-17 76.25 0.92 0.06 ok
7RMG_R P25103 Substance-P receptor EM 3.00 2021-07-27 78.38 0.92 0.06 ok
7RMH_R P25103 Substance-P receptor EM 3.10 2021-07-27 78.38 0.93 0.06 ok
7RMI_R P25103 Substance-P receptor EM 3.20 2021-07-27 78.38 0.93 0.06 ok
7RHG_B Q14028 Cyclic nucleotide-gated cation channel bet EM 2.88 2021-07-17 57.66 0.90 0.06 ok
7RH9_B Q14028 Cyclic nucleotide-gated cation channel bet EM 2.61 2021-07-16 57.66 0.91 0.05 ok
7Q2U_AAA P49773 Histidine triad nucleotide-binding protein X-ray 2.27 2021-10-26 96.19 0.95 0.05 ok
7F58_G P59768 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-06-21 89.56 0.95 0.05 ok
7RN6_A O60674 Tyrosine-protein kinase JAK2 X-ray 1.50 2021-07-29 86.88 0.94 0.05 ok
7P3V_A P15056 Serine/threonine-protein kinase B-raf X-ray 2.37 2021-07-08 66.38 0.93 0.05 ok
7F53_R P32245 Melanocortin receptor 4 EM 3.00 2021-06-21 80.12 0.94 0.05 ok
7F58_R P32245 Melanocortin receptor 4 EM 3.10 2021-06-21 80.12 0.94 0.05 ok
7F54_R P32245 Melanocortin receptor 4 EM 3.00 2021-06-21 80.12 0.94 0.05 ok
7F55_R P32245 Melanocortin receptor 4 EM 3.10 2021-06-21 80.12 0.94 0.05 ok
7M2K_B P0CG47 Ubiquitin X-ray 2.47 2021-03-16 93.44 0.95 0.04 ok
7RHI_B Q14028 Cyclic nucleotide-gated cation channel bet EM 3.31 2021-07-17 57.66 0.92 0.04 ok
7KLV_A Q12931 Heat shock protein 75 kDa, mitochondrial, EM 3.10 2020-11-01 86.00 0.95 0.04 ok
7S5G_B Q8NBP7 Proprotein convertase subtilisin/kexin typ X-ray 2.04 2021-09-10 85.19 0.96 0.04 ok
7ARX_B P48740 Mannan-binding lectin serine protease 1 X-ray 2.42 2020-10-26 90.44 0.96 0.04 ok
7KLU_A Q12931 Heat shock protein 75 kDa, mitochondrial, EM 3.50 2020-11-01 86.00 0.96 0.04 ok
6YR6_A P31947 14-3-3 protein sigma X-ray 1.75 2020-04-19 92.88 0.96 0.03 ok
7DTG_A P20700 Lamin-B1 X-ray 3.60 2021-01-05 82.44 0.96 0.03 ok
7VFU_A Q00975 Voltage-dependent N-type calcium channel s EM 3.00 2021-09-13 59.91 0.94 0.03 ok
7S1N_A P53779 Mitogen-activated protein kinase 10 X-ray 2.11 2021-09-02 79.31 0.96 0.03 ok
7NV1_A Q9UBT6 DNA polymerase kappa EM 6.40 2021-03-15 70.50 0.95 0.03 ok
7VFS_A Q00975 Voltage-dependent N-type calcium channel s EM 2.80 2021-09-13 59.91 0.95 0.03 ok
6YR7_A P31947 14-3-3 protein sigma X-ray 2.10 2020-04-19 92.88 0.97 0.03 ok
7VFW_A Q00975 Voltage-dependent N-type calcium channel s EM 3.30 2021-09-13 59.91 0.95 0.03 ok
7VFV_A Q00975 Voltage-dependent N-type calcium channel s EM 3.00 2021-09-13 59.91 0.95 0.03 ok
7M2K_A P49427 Ubiquitin-conjugating enzyme E2 R1 X-ray 2.47 2021-03-16 85.06 0.97 0.03 ok
6YR5_A P31947 14-3-3 protein sigma X-ray 2.25 2020-04-19 92.88 0.97 0.03 ok
7S5H_B Q8NBP7 Proprotein convertase subtilisin/kexin typ X-ray 1.27 2021-09-10 85.19 0.97 0.03 ok
7EKG_A Q9BYF1 Angiotensin-converting enzyme 2 X-ray 2.63 2021-04-05 90.69 0.97 0.03 ok
7EKC_A Q9BYF1 Angiotensin-converting enzyme 2 X-ray 2.80 2021-04-05 90.69 0.97 0.03 ok
7EKH_A Q9BYF1 Angiotensin-converting enzyme 2 X-ray 2.40 2021-04-05 90.69 0.97 0.03 ok
7EKF_A Q9BYF1 Angiotensin-converting enzyme 2 X-ray 2.85 2021-04-05 90.69 0.97 0.02 ok
7RA5_A P24941 Cyclin-dependent kinase 2 X-ray 1.67 2021-06-30 88.44 0.97 0.02 ok
7EKE_A Q9BYF1 Angiotensin-converting enzyme 2 X-ray 2.70 2021-04-05 90.69 0.97 0.02 ok
7MK1_A O95786 Antiviral innate immune response receptor X-ray 1.90 2021-04-21 85.19 0.97 0.02 ok
7NV1_B P12004 Proliferating cell nuclear antigen EM 6.40 2021-03-15 94.31 0.98 0.02 ok
7VFW_D Q02641 Voltage-dependent L-type calcium channel s EM 3.30 2021-09-13 69.00 0.97 0.02 ok
7VFV_D Q02641 Voltage-dependent L-type calcium channel s EM 3.00 2021-09-13 69.00 0.97 0.02 ok
7N13_A P36639 7,8-dihydro-8-oxoguanine triphosphatase X-ray 1.59 2021-05-26 97.19 0.98 0.02 ok
7VFS_D Q02641 Voltage-dependent L-type calcium channel s EM 2.80 2021-09-13 69.00 0.98 0.01 ok
7APS_A Q13451 Peptidyl-prolyl cis-trans isomerase FKBP5 X-ray 0.94 2020-10-19 92.50 0.99 0.01 ok
7L4X_B Q96MU7 YTH domain-containing protein 1 X-ray 1.79 2020-12-21 60.34 0.98 0.01 ok
7L4Y_B Q96MU7 YTH domain-containing protein 1 X-ray 1.79 2020-12-21 60.34 0.98 0.01 ok
7ALS_A O00214 Galectin-8 X-ray 1.35 2020-10-07 90.69 0.99 0.01 ok
7RMH_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-07-27 97.06 0.99 0.01 ok
7S5H_A Q8NBP7 Pro-peptide from Proprotein convertase sub X-ray 1.27 2021-09-10 85.19 0.99 0.01 ok
7S5G_A Q8NBP7 Propeptide of Proprotein convertase subtil X-ray 2.04 2021-09-10 85.19 0.99 0.01 ok
7VFU_D Q02641 Voltage-dependent L-type calcium channel s EM 3.00 2021-09-13 69.00 0.99 0.01 ok
7N03_A P36639 7,8-dihydro-8-oxoguanine triphosphatase X-ray 1.13 2021-05-24 97.19 0.99 0.01 ok
7RMI_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.20 2021-07-27 97.06 0.99 0.01 ok
7RXV_A P31153 S-adenosylmethionine synthase isoform type X-ray 1.07 2021-08-23 96.06 0.99 0.01 ok
6XRN_A P48736 Phosphatidylinositol 4,5-bisphosphate 3-ki X-ray 2.96 2020-07-13 87.81 0.99 0.01 ok
7VFS_B P54289 Voltage-dependent calcium channel subunit EM 2.80 2021-09-13 86.56 0.99 0.01 ok
7EG1_A Q14432 cGMP-inhibited 3',5'-cyclic phosphodiester EM 3.20 2021-03-23 60.25 0.99 0.01 ok
7B0V_A P27338 Amine oxidase [flavin-containing] B X-ray 2.30 2020-11-23 95.62 0.99 0.01 ok
7B0Z_A P27338 Amine oxidase [flavin-containing] B X-ray 2.10 2020-11-23 95.62 0.99 0.01 ok
7RMG_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-07-27 97.06 0.99 0.01 ok
7VFW_B P54289 Voltage-dependent calcium channel subunit EM 3.30 2021-09-13 86.56 0.99 0.00 ok
7VFV_B P54289 Voltage-dependent calcium channel subunit EM 3.00 2021-09-13 86.56 0.99 0.00 ok
7VFU_B P54289 Voltage-dependent calcium channel subunit EM 3.00 2021-09-13 86.56 0.99 0.00 ok
7F55_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-06-21 97.06 1.00 0.00 ok
7F54_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-06-21 97.06 1.00 0.00 ok
7F58_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.10 2021-06-21 97.06 1.00 0.00 ok
7F53_B P62873 Guanine nucleotide-binding protein G(I)/G( EM 3.00 2021-06-21 97.06 1.00 0.00 ok
7AM9_A P11172 Uridine 5'-monophosphate synthase X-ray 0.99 2020-10-08 92.12 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.