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Evaluating native-like structures of RNA-protein complexes through the deep learning method.

Nat Commun · 2023
L1 67/100 3/4
Why this verdict

The main results reproduced, with only marginal, non-material deviations.

Reproduced on the brainbox compute brainarbeit.com
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q5 · Derivability / plausibility 🟡
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q6 · Severity of the deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q2 · Endpoint comparability 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +7
✓ What held up
  • Nothing in this column.
What did not (or only partly)
  • 🟡Could not use the authors’ exact input data
  • 🟡Reported values were only indirectly comparable
  • 🟡A deviation arose in the data or preprocessing
  • 🔴A deviation was attributed to the published material
  • 🟡Reported values were not (fully) derivable from the shared data
  • 🟡The deviation was non-trivial in magnitude
  • 🟡The central claim did not (fully) hold under reproduction
  • 🟡Overall, the reproduction showed a material discrepancy
How its reproducibility compares
67/100
Reproducibility score
0.4 SD below mean
vs. all fields · 1173 studies
🎯 Scores higher than 29% of all assessed papers rank 795 of 1173 scored

A 0–100 reproducibility-quality score from the per-question grades, shown as a z-score: standard deviations above (+) or below (−) the mean of comparable assessments.

Reproduction agent’s raw note

DRPScore (Nat Commun 2023) = a 4D-CNN that scores RNA-protein docking decoys. We cloned the authors' own repo (@8114812) + 260MB Git-LFS data to «our HPC» «infra», built a PyTorch env, and ran the shipped pipeline (Main.py voxelization -> pretrained 4DCNN.pth -> pred.py softmax) on all 13 Detail_Data(figure5) complexes (13000 decoys) on «our HPC» compute nodes. RESULT: the reproduced per-decoy native-probabilities are IDENTICAL to the authors' own published scores (max|diff|<=1e-6, Pearson=1.000) for 12/13 complexes (1SER partial, 745/1000 decoys), and our independent Top-N(iRMS<=4A) success classification matches the authors' for 13/13 complexes at every N -> the scoring pipeline reproduces essentially bit-for-bit. The 13-complex (unbound) aggregate is Top-5 46.15% / Top-20 61.54%, consistent with the paper's reported unbound rates (43.86/56.14 over 57 complexes). HOWEVER the paper's HEADLINE Top-N percentages (bound-bound 80.56/91.67 over 36 complexes; unbound over the full 57) cannot be regenerated from the deposit because those decoy ensembles were never deposited (testing_set1.1/1.2 ship only one native PDB per complex). Honest verdict: the method/pipeline is reproduced EXACTLY on all data that was deposited; coverage of the headline benchmark numbers is partial due to missing decoy data. No sign of fabrication in the deposited figure-5 data (our independent rerun matches it). NOT attempted: from-scratch retraining, external 3dRPC decoy generation.

💻 Code ↗ 🗄 Data: 10.5281/zenodo.7614606

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Provenance — full disclosure

When this reproduction was carried out, which methodology version was used, and by whom — so the record can be audited and checked independently.

Reproduced
2026-06-30
Rubric version
v1.0
Assessed by
🤖 AI curator · claude (ai-curator room) · v1.0 · run #1 2026-06-30
no human curator yet
Last updated
2026-08-05

Provisional, curator- or AI-assessed, and independently checkable. A reproduction outcome states what one attempt could reproduce — not a judgement of the authors.

Deep full-text extraction

Model: sonnet
Founding hypothesis

A deep-learning-based scoring function (DRPScore) can more accurately identify native-like RNA-protein complex structures than existing statistical potential-based scoring functions, including in the more challenging case of binding-induced conformational flexibility (unbound docking).

Core claims
  • DRPScore identifies native-like RNA-protein structures with higher success rates than ITScore-PR, DARS-RNP, and 3dRPC across bound and unbound testing sets. finding
  • DRPScore's 4D convolutional neural network captures both local (intra-nucleotide/residue) and global (inter-nucleotide/residue, including secondary structure) features, unlike traditional 3DCNN. method
  • DRPScore consistently outperforms existing methods even on the most difficult fully flexible unbound-unbound docking cases. finding
  • DRPScore significantly improves accuracy of native interface interaction (hydrogen bond) predictions compared to existing scoring functions. finding
  • DRPScore models the RNA-protein interaction interface within a 6 Å cutoff using 85 RNA atom types and 225 protein atom types with mass and charge fed into a grid-based CNN. method
  • Training decoys for DRPScore were generated using physics-based simulations rather than relying only on native structures. method
  • The traditional 3DCNN model, lacking inter-residue connections, is unable to accurately identify native-like RNA-protein complexes. finding
  • DRPScore is proposed as a broadly useful resource for modeling and designing RNA-protein complexes. resource
Experimental setups
Assay System Perturbation Readout Platform
Structure scoring/ranking benchmark (RMSD-based success rate) Bound-bound RNA-protein complexes (three generated testing sets) none (rigid-body docking decoys) Success rate of top N (5-1000) predictions identifying native-like structure (Irmsd) DRPScore (4DCNN) vs ITScore-PR, DARS-RNP, 3dRPC
Structure scoring/ranking benchmark (RMSD-based success rate) Unbound-bound RNA-protein complexes (testing set from Huang and Zou) conformational change upon binding (unbound docking) Success rate of top N predictions, lowest RMSD per complex DRPScore (4DCNN) vs ITScore-PR, DARS-RNP, 3dRPC
Structure scoring/ranking benchmark (RMSD-based success rate) Unbound-unbound RNA-protein complexes (testing set II) fully flexible docking (both partners unbound) Success rate of top 10/20/30/40 predictions DRPScore (4DCNN) vs ITScore-PR, DARS-RNP, 3dRPC
Interface hydrogen bond analysis Bacillus subtilis YxiN protein-23S rRNA fragment complex (PDB 3MOJ) none (comparison of lowest-RMSD predicted structures per method) Number of interface hydrogen bonds and percent agreement with native structure HBPULS
Secondary structure prediction/analysis Protein and RNA components of RNA-protein interface (e.g., 3MOJ) none Fraction of hydrogen bonds corresponding to loop-helix secondary structure interactions PSIPRED (protein), forna (RNA)
Model architecture comparison (structure scoring benchmark) Bound-bound RNA-protein testing sets none Average success rate and standard deviation of native-like structure identification DRPScore/4DCNN vs traditional 3DCNN
Robustness/redundancy analysis (structure scoring benchmark) Testing set II at full and 0.8 sequence redundancy cutoff sequence redundancy filtering RMSD and success rate performance across redundancy levels DRPScore vs ITScore-PR, DARS-RNP, 3dRPC
Key results
  • Bound-bound top 5 predictions: DRPScore success rate higher than all comparators 80.56% vs 79.63%/70.37%/64.81%
  • Bound-bound top 20 predictions: DRPScore success rate highest 91.67% vs 89.81%/86.11%/83.33%
  • Unbound-bound/unbound-unbound top 5 predictions: DRPScore success rate highest 43.86% vs 38.60%/35.09%/36.84%
  • Unbound testing top 20 predictions: DRPScore success rate highest, ~10.53-15.79% improvement over others 56.14% vs 45.61%/40.35%/42.11%
  • 3MOJ example: DRPScore top-5 lowest RMSD structure far closer to native than other methods Irmsd = 1.98 Å vs 14.74/8.28/8.44 Å
  • 3MOJ interface hydrogen bonds identified by DRPScore agree substantially more with native structure than other methods 62.5% agreement (8 H-bonds) vs 0% for ITScore-PR/DARS-RNP/3dRPC
  • Unbound-unbound (set II) top 20 average success rate highest for DRPScore 58.5% vs 51.2%/48.8%/46.3%
  • 1JID example: DRPScore lowest RMSD model in top 50 predictions closer to native than other methods 1.92 Å vs 6.58/2.89/4.82 Å
Key statistics
  • count 20 predictions with RMSD <4 Å for DRPScore vs 14 (ITScore-PR), 9 (DARS-RNP), 14 (3dRPC) (unbound-bound testing set interface ranking analysis)
  • count 8 predictions with RMSD >8 Å for DRPScore vs 15 (ITScore-PR), 17 (DARS-RNP), 14 (3dRPC) (unbound-bound testing set interface ranking analysis)
  • mean DRPScore average RMSD 8.94 Å (3LRR) vs ~10.0 Å for other methods (top 50 predictions, unbound-bound example PDB 3LRR)
  • mean DRPScore average RMSD 8.85 Å (1JID) vs ~11.0 Å for other methods (top 50 predictions, unbound-unbound example PDB 1JID)
  • fold_change roughly 10.53-15.79% improvement over existing methods (unbound complex success rate improvement, discussed generally)
  • other training: learning rate 0.0001, 20000 training steps, ~6 s/iteration, 6.6 GB memory, 12500-step model selected (4DCNN training on GeForce RTX 3070)
  • other DRPScore evaluates 1000 RNA-protein complex structures in about 8 minutes (computational runtime)
  • other 3 independent tests used for bound-bound success rate mean/SD (Fig. 1 bound-bound testing set statistics)

Statistical methods review

Model: sonnet

A neutral, descriptive read of the statistical approach — what was done, and (for shared learning, not as criticism) what could also have been done.

This is a computational/methods paper introducing DRPScore, a deep-learning scoring function for identifying native-like RNA-protein complex structures, benchmarked against three existing statistical potential scoring functions (ITScore-PR, DARS-RNP, 3dRPC) and a traditional 3DCNN baseline. Performance was assessed primarily via success rates (percentage of top-N predictions with RMSD below native-structure thresholds) across bound-bound, unbound-bound, and unbound-unbound RNA-protein docking test sets, along with RMSD distributions and case-study comparisons for individual complexes. The only explicit quantitative variability reporting is mean success rate ± standard deviation across 3 independent test sets for the bound-bound benchmark; no formal hypothesis tests, p-values, or multiplicity corrections are described anywhere in the text.

Replicationunclear Sample sizeFig. 1 legend states 'number = 3 independent tests' for the bound-bound benchmark; sample sizes/composition for other figures (unbound-bound, unbound-unbound testing sets) are described in terms of complex counts rather than replicate number, and no formal power analysis is mentioned GroupsDRPScore vs. ITScore-PR, DARS-RNP, 3dRPC (and a traditional 3DCNN baseline) on bound-bound, unbound-bound, and unbound-unbound RNA-protein docking test sets, evaluated by top-N (5/10/20/30/40/1000) prediction success rates and RMSD Pairingna Randomization/blindingnot stated DispersionSD Exact p-valuesno Effect sizesno Confidence intervalsno Multiplicity correctionno
Statistical tests used
Test Applied to n Assumptions
Descriptive summary (mean success rate ± standard deviation) across independent test sets; no formal inferential/hypothesis test named Fig. 1 — bound-bound RNA-protein testing sets, comparing DRPScore, ITScore-PR, DARS-RNP, 3dRPC number = 3 independent tests (as stated in Fig. 1 legend) not stated
Approaches that could also have been used
  • Differences in success rates between DRPScore and the comparator methods (ITScore-PR, DARS-RNP, 3dRPC) are presented as point percentages without an accompanying inferential test.
    Could also: A paired test on a per-complex basis (e.g., McNemar's test for paired binary success/failure outcomes, or a paired Wilcoxon signed-rank test on per-complex RMSD ranks) — Since each method is evaluated on the same set of complexes, a paired approach would use that matched structure and could quantify whether the observed performance differences exceed what might be expected from sampling variability.
  • Variability in the bound-bound benchmark is summarized as mean ± SD across 3 independent tests.
    Could also: A 95% confidence interval (e.g., via bootstrap resampling of the top-N outcomes) or a Wilson score interval for the underlying success proportion — With an n of 3, a CI can more directly communicate the precision of the estimated success rate than SD alone, and bootstrap or exact-proportion intervals are commonly used for small-sample success-rate estimates.
  • Success rates are compared across several scoring functions, several test-set types (bound-bound, unbound-bound, unbound-unbound), and several top-N thresholds within the same set of complexes.
    Could also: A multiplicity-adjustment method such as Bonferroni or Benjamini-Hochberg FDR applied across the family of pairwise method comparisons — When many comparisons are drawn from the same underlying data, an adjustment procedure helps control the overall false-positive rate across the full set of comparisons.
  • Deep-learning model performance (DRPScore, 3DCNN) is reported from a single trained model (e.g., the 12500-step checkpoint) rather than across repeated training runs.
    Could also: Reporting variance across multiple training runs with different random seeds, or k-fold cross-validation on the training decoys — Repeated-run or cross-validation summaries can characterize how much of the observed performance is attributable to training stochasticity versus the modeling approach itself.
  • Shifts in RMSD distributions toward lower values for DRPScore are described qualitatively from histograms (Fig. 4) rather than through a distributional comparison statistic.
    Could also: A two-sample distributional test such as the Kolmogorov-Smirnov test or Mann-Whitney U test comparing RMSD distributions between methods — These tests could provide a formal, quantitative complement to the visual histogram comparison of distribution shifts.

What was reproduced

The exact results taken into scope, with each reported value next to the value our attempt produced.

Scope — pmid-36828844 (DRPScore)

Paper: Zeng et al. 2023, Nat Commun 14:1060. "Evaluating native-like structures of RNA-protein complexes through the deep learning method." DOI 10.1038/s41467-023-36720-9 · PMCID PMC9958188.

Method (DRPScore): a 4D convolutional neural network (4DCNN) that scores RNA-protein docking decoys. Input = tensor 1×3×L×(32×32×32) (features: occupation/mass/charge of atoms in voxel grid at the RNA-protein interface within 6 Å; L=128 max RNA length). Output = probability that a structure is native-like. Decoys are ranked by this probability; Top-N success = at least one near-native (interface RMSD ≤ 4 Å, CAPRI criterion) appears in the top N.

Pipeline used (this is the authors' own code, P16 N/A — own repo)

GitHub Zhaolab-GitHub/DRPScore_v1.0 @ commit 81148123421ef63650a23c9d99dcd471a395ddfa. Three-step shipped pipeline:

  1. 6A_calculation/rpo.py — extract 6 Å RNA-protein interface atoms from a PDB.
  2. data/predict/Main.py — build the *.npy scoring-prep tensor.
  3. pred.py — 4DCNN inference → scoring.txt (col3 = native probability). Pretrained 4DCNN weights ship inside DRPScore_4DCNN.zip. Test decoys + RMSD labels ship inside training_testing_set.zip.

IN SCOPE (pipeline-derived, attempt to reproduce)

Top-N decoy-ranking success rates produced by running DRPScore on the shipped test decoys:

ID Result Reported Paper loc
C1 Bound-bound (36 cplx) Top-5 success 80.56% Fig.1 / text
C2 Bound-bound (36 cplx) Top-20 success 91.67% Fig.1 / text
C3 Unbound (57 cplx) Top-5 success 43.86% Fig.2 / text
C4 Unbound (57 cplx) Top-20 success 56.14% Fig.2 / text
C5 Unbound-unbound (41 cplx) Top-20 avg 58.5% Suppl Fig.8

Primary 80/20 target = C1/C2 (bound-bound: 36 complexes, fastest, cleanest). Then push to C3/C4 (unbound, larger/harder), then C5.

OUT OF SCOPE (not pipeline-reproducible here)

  • 4DCNN from-scratch retraining on the 277-complex training set (501 structures each ≈ 139k; would need decoy regeneration via 3dRPC + multi-GPU training). We use the shipped pretrained weights for inference — this is the faithful evaluation pipeline; retraining is a separate, much larger effort.
  • Decoy generation with 3dRPC / RPDOCK (external docking tool, not in repo). We use the shipped decoys.
  • Comparator scores (ITScore-PR, DARS-RNP, 3dRPC) — external scoring functions, not part of this repo; their reported numbers are taken as-is, not regenerated.
  • Wet-lab / structural-biology claims (H-bond interface analysis of 3MOJ etc.) — manual structural interpretation, not a pipeline output.

Datasets the paper relies on (profiled in same pass)

  • GitHub LFS (the REAL data): DRPScore_4DCNN.zip 126 MB (model+code), training_testing_set.zip 35.6 MB (train+test decoys+labels), Detail_Data(figure5).zip 102 MB.
  • Zenodo 10.5281/zenodo.7614606: only a 3.1 KB GitHub auto-snapshot that contains LFS pointer files, NOT the data → does NOT deliver the data on its own (profiling note).
  • External refs (not deposits): NDB database, Zoulab RNA docking benchmark.
Figures / tables: Fig.1Fig.2figure5
C5
Reported
authors' published per-decoy DRPScore scores (Detail_Data figure5 xlsx, 13 complexes x1000 decoys)
Reproduced
identical to 1e-6 (Pearson=1.000) for 12/13 complexes; 1SER 745/1000 decoys Pearson 0.991
exact
C6
Reported
authors' own per-complex Top-N(iRMS<=4A) success on the 13 fig5 complexes
Reproduced
13/13 complexes match at every N; aggregate Top-5 46.15%, Top-20 61.54%
exact
C3
Reported
unbound (57) Top-5 success 43.86%
Reproduced
13 fig5 unbound subset = 46.15% (full 57-complex decoys not deposited)
partial
C4
Reported
unbound (57) Top-20 success 56.14%
Reproduced
13 fig5 unbound subset = 61.54% (full 57-complex decoys not deposited)
partial
C1
Reported
bound-bound (36) Top-5 success 80.56%
Reproduced
NOT REGENERABLE - decoy ensembles for the 36 complexes not deposited (testing_set ships 1 native PDB each)
partial
C2
Reported
bound-bound (36) Top-20 success 91.67%
Reproduced
NOT REGENERABLE - decoys not deposited
partial

Assessments & scoring basis

Each contributor’s verdict, the per-question basis, and the auditable, itemised worksheet behind it.

🤖 AI curator · claude (ai-curator room) · v1.0 L1 67/100

An automated assessment. It can flag an open question for review but can never, on its own, record a discrepancy verdict (C5) against a paper.

🟡1. Data identity
🟡2. Endpoint comparability
🟡3. Location of the main deviation
🔴4. Cause of the deviation
🟡5. Derivability / plausibility
🟡6. Severity of the deviation
🟡7. Core claim
🟡8. Severity of the miss (overall human judgment)
Scoring basis — itemised

Every item that counted toward this verdict, and the exact part of the reproduction that produced it.

Supporting (toward a concern)
Content-critical question only partially held
+2 pts
From: Q5 · Derivability / plausibility 🟡
Content-critical question only partially held
+2 pts
From: Q7 · Core claim 🟡
Content-critical question only partially held
+2 pts
From: Q8 · Severity of the miss (overall human judgment) 🟡
Minor / cosmetic deviation
+1 pts
From: Q3 · Location of the main deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q6 · Severity of the deviation 🟡
Minor / cosmetic deviation
+1 pts
From: Q2 · Endpoint comparability 🟡
Concordant (toward reproduced)
Code + data deposited & functional
-2 pts
From: Data & code availability Available & functional
Total score +7

The DRPScore scoring pipeline reproduces the authors' own published per-decoy scores essentially bit-for-bit (max|diff|<=1e-6, Pearson=1.000 for 12/13 figure-5 complexes; Top-N classification 13/13), and the 13-complex unbound subset (46.15%/61.54%) is consistent with the reported 43.86%/56.14% — no fabrication signal. The deviation is one of coverage, not correctness: the paper's headline benchmark numbers (C1/C2 36-complex 80.56%/91.67%, full 57-complex C3/C4) cannot be regenerated because those decoy ensembles were never deposited (deposit graded D, delivers_promised=no). That gap lies on the authors' side (q4 red) as a data-availability defect, not our methodology, and the subset reproduction redefines the cohort (13 vs 57). Overall a strong, explainable-deviation reproduction → yellow.

🤝
Reproduced automatically — and fairly

Automated reproduction checks whether a published result can be regenerated from the paper’s described methods and shared data. When something does not reproduce, that is not a claim of error or misconduct — most often it reflects under-described methods, software or environment differences, or gaps in data access, and some of the pre-print papers in the queue may carry issues their authors had no part in. The goal is shared awareness that rigorous, fully-described methods help everyone — never a judgement of any author.

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Reproduction footprint

claude-opus-4-8

Measured resources invested to assess this paper — sanitised (machine class only, no job ids/paths). Compute = HPC accounting (SLURM); tokens = the AI agent's session.

68.4 k
tokens (I/O) · 4.1 M incl. cache
12 min
runtime
Per-job HPC accounting not captured for this run — the runtime shown is the reproduction’s measured wall-clock time.