Kalipatnapu commited on
Senba release: mars-fm-e010-a07350-exactlag-128x32-20260825-s1-v1 (validation-only)
Browse files- LICENSE +25 -0
- README.md +208 -0
- inference_example.py +186 -0
- protocols/MARS_FM_ANCHOR08_FULL_VALIDATION_V1_PROTOCOL.md +125 -0
- protocols/MARS_FM_EPOCH_SWEEP_V1_PROTOCOL.md +108 -0
- protocols/MARS_FM_EQUILIBRIUM_SUITE_PROTOCOL.md +37 -0
- protocols/MARS_FM_MDCATH_ADAPTATION_PROTOCOL.md +88 -0
- receipts/equilibrium-suite-comparison.json +616 -0
- receipts/full-transition-comparison.json +284 -0
- receipts/head-to-head-vs-previous-senba.json +284 -0
- receipts/interpolation-config.json +1 -0
- receipts/interpolation-result.json +1 -0
- receipts/parent/training-config.json +1 -0
- receipts/parent/training-result.json +1 -0
- receipts/replications/seed2/compact-transition-comparison.json +104 -0
- receipts/replications/seed2/interpolation-result.json +1 -0
- receipts/replications/seed2/parent-result.json +1 -0
- receipts/replications/seed3/compact-transition-comparison.json +104 -0
- receipts/replications/seed3/interpolation-result.json +1 -0
- receipts/replications/seed3/parent-result.json +1 -0
- receipts/selection-v2.json +120 -0
- release-manifest.json +121 -0
- senba.ckpt +3 -0
LICENSE
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MIT License
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Senba adaptation: Copyright (c) 2026 Paper Crane (papercrane.bio)
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MarS-FM source model and code: Copyright (c) 2026 Valence Labs
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Permission is hereby granted, free of charge, to any person obtaining a copy
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of this software and associated documentation files (the "Software"), to deal
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in the Software without restriction, including without limitation the rights
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to use, copy, modify, merge, publish, distribute, sublicense, and/or sell
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copies of the Software, and to permit persons to whom the Software is
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furnished to do so, subject to the following conditions:
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The above copyright notice and this permission notice shall be included in all
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copies or substantial portions of the Software.
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THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
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IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY,
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FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE
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AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER
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LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM,
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OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE
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SOFTWARE.
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The weights were adapted on mdCATH (compsciencelab/mdCATH), which is
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distributed under CC BY 4.0. Attribute mdCATH when you use these weights.
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README.md
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---
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license: mit
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base_model: valencelabs/mars-fm
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datasets:
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- compsciencelab/mdCATH
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library_name: pytorch
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tags:
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- protein-dynamics
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- molecular-dynamics
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- flow-matching
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- mars-fm
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- mdcath
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- biology
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- pytorch
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---
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# Senba
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Senba is a source-anchored adaptation of [MarS-FM](https://github.com/valence-labs/mars-fm)
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(Valence Labs, ICLR 2026) for mdCATH backbone transitions at 450 K and one 50-frame lag.
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It is published as a **validation-stage candidate** together with the selection receipt, every
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comparison, and the preregistered protocols, so the claim below can be audited.
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**Claim, exactly:** on the complete 28-domain sequence-length-eligible mdCATH validation panel,
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Senba improves ensemble-mean endpoint C-alpha RMSD over source MarS-FM by 0.0326 Å (protein-bootstrap
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95% CI [0.0253, 0.0401]; 27/28 domains improved), improves over coordinate persistence by 0.436 Å
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(CI [0.203, 0.681]; 22/28), and keeps all seven frozen equilibrium-retention observables within
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their limits on the eight-domain equilibrium suite. The gain reproduced across three training seeds.
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**Boundary, exactly:** this is not test-set evidence (the 495-domain standard mdCATH test partition
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remains unopened; every receipt records `test_records_opened = 0`), not a state-of-the-art or
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field-leadership claim (the only matched baselines are source MarS-FM and persistence), not
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physical-time kinetics, rare-event, or long-timescale evidence (one lag only), not all-atom
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validation (C-alpha metrics), not broad unseen-protein generalization (28 validation domains at or
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below 256 residues), and not a final model.
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Release page: <https://senba.papercrane.bio/>
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## Identity
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| Field | Value |
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| --- | --- |
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| Run | `mars-fm-e010-a07350-exactlag-128x32-20260825-s1-v1` |
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| Checkpoint | `senba.ckpt` · 136,711,098 bytes · SHA-256 `f02dcf6a97848c834e3c0be7d848c1068d1d0eb7976d8d6bcfbc98d4114e9c7c` |
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| Base model | [`valencelabs/mars-fm`](https://huggingface.co/valencelabs/mars-fm) revision `1e957cd4b9f1a054ceb0c2104f40ba6f3cc0d8d0`, `mars_fm.ckpt` SHA-256 `f56794cc5d1a8e5263031944f932384dd785fe945553612fe76fe1e9191fa879` |
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| Source code | [`valence-labs/mars-fm`](https://github.com/valence-labs/mars-fm) commit `4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946` |
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| Architecture | Unchanged MarS-FM; 34,152,521 parameters, all trainable during adaptation |
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| Adaptation data | mdCATH, bounded development subset of 128 train and 32 validation domains (manifest `sha256:163ab0043d86b5a2731e1b1a233af27fb069049897d657fd5c39bd54b1343b3f`), 450 K replicas |
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| Objective | Observed same-replica frame pairs separated by exactly 50 frames (`exact_lag`), cluster-balanced starts, no replica crossing |
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| Anchoring | Source-checkpoint weight interpolation, α = 0.0735 (7.35% of the fine-tuning displacement retained) |
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| Frozen | 2026-08-25 |
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| Test records opened | 0 |
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The checkpoint is a PyTorch Lightning checkpoint. Its `hyper_parameters` contain an
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`argparse.Namespace`, so loading under `torch>=2.6` requires
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`torch.serialization.add_safe_globals([argparse.Namespace])` (the example script does this).
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## How it was made
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1. **Parent fine-tune.** All MarS-FM parameters were fine-tuned from the pinned source checkpoint
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for 10 epochs (160 optimizer updates, 30,720 sampled exact-lag transitions), batch size 8
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domains, learning rate 3e-6, fresh Adam, seed 20260825, on one NVIDIA H100 in 121.80 s (peak
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64.7 GB allocated). Validation loss on a fixed transition population with replayed flow
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randomness moved from the replayed source value 1.724479 to 1.693136. Parent run
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`mars-fm-epoch-sweep-e010-exactlag-128x32-20260825-s1-v1`, checkpoint SHA-256
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`1bd5c20b5f3aa8587dce6440af6580f0c2def98d0b868a39969ef854bd729a25`.
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2. **Anchoring.** The parent damaged the source model's equilibrium ensembles and was rejected as a
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deployable candidate. Senba is `source + 0.0735 · (parent − source)` in weight space.
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3. **Selection.** α was chosen on the frozen epoch-sweep protocol, then the candidate had to pass the
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full-panel transition comparison and the equilibrium-retention suite without any change to the
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checkpoint, inference settings, metrics, or population.
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## Evidence
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All intervals are protein-level bootstraps with 100,000 resamples. Positive values mean Senba's
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sampled endpoints are closer to the observed endpoint than the baseline's. Inference used 10 ODE
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steps, four starts per replica, four samples per start, five 450 K replicas, lag 50.
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### Full eligible validation panel (28 domains, ≤256 residues)
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| Comparison | Ensemble-mean endpoint C-alpha RMSD improvement | 95% CI | Domains improved |
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| --- | --- | --- | --- |
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| vs source MarS-FM | +0.0326 Å | [0.0253, 0.0401] | 27 / 28 |
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| vs coordinate persistence | +0.436 Å | [0.203, 0.681] | 22 / 28 |
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| vs previous Senba (5-epoch, α = 0.08) | +0.00216 Å | [0.00086, 0.00345] | 22 / 28 |
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Secondary summaries on the same outputs: best-of-k RMSD improvement vs source +0.0372 Å,
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single-sample RMSD improvement vs source +0.0689 Å, displacement-magnitude MAE improvement
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+0.0292 Å, direction-cosine improvement +0.0014. Per-domain rows are in
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`receipts/full-transition-comparison.json`.
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### Equilibrium retention (8 domains, official tree sampling, 500 samples)
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Degradation is measured in each observable's unfavorable direction against source MarS-FM;
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negative values are improvements. Limits were frozen before any candidate output existed.
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| Observable | Mean degradation | 95% CI | Mean limit | Worst domain / limit | Pass |
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| --- | --- | --- | --- | --- | --- |
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| DCCM MAE | −0.000660 | [−0.001625, 0.000285] | 0.005 | 0.001768 / 0.01 | ✓ |
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| Native-contact fraction W1 | +0.000271 | [−0.001594, 0.001946] | 0.015 | 0.003055 / 0.03 | ✓ |
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| Pairwise RMSD W1 (Å) | −0.0437 | [−0.1260, 0.0493] | 0.25 | 0.2076 / 0.5 | ✓ |
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| PCA subspace RMSIP | +0.00416 | [−0.00023, 0.01075] | 0.03 | 0.02536 / 0.06 | ✓ |
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| Clash fraction | −0.0000012 | [−0.0000246, 0.0000225] | 0.0005 | 0.0000575 / 0.001 | ✓ |
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| Radius of gyration W1 (Å) | −0.0422 | [−0.0775, −0.0080] | 0.15 | 0.0319 / 0.3 | ✓ |
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| RMSF RMSE (Å) | −0.0222 | [−0.0776, 0.0396] | 0.15 | 0.1471 / 0.3 | ✓ |
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### Replication (three independently trained parents, 8-domain compact panel)
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| Parent seed | Gain vs source | 95% CI | Domains improved | Matched difference vs previous Senba |
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| --- | --- | --- | --- | --- |
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| 1 (20260825) | +0.0301 Å | [0.0184, 0.0431] | 8 / 8 | +0.00308 Å |
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| 2 (20260826) | +0.0229 Å | [0.0133, 0.0343] | 8 / 8 | −0.00110 Å |
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| 3 (20260827) | +0.0290 Å | [0.0183, 0.0386] | 8 / 8 | +0.00557 Å |
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Three-seed mean gain over source: +0.0273 Å. Mean matched difference vs the previous Senba:
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+0.00252 Å. The seed-2 difference is negative and its interval crosses zero, so the correct reading
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is a modest average improvement over the previous checkpoint, not a uniform win at every seed.
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### Negative results that remain part of the evidence
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The fully fine-tuned exact-lag parents (5, 10, 20, 40, 80, and 160 epochs), the 25% and 50%
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hybrid objectives, and the larger anchors (α ≥ 0.1) either damaged equilibrium retention or lost
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the transition gain. They are recorded in the protocols and are not substitutes for Senba.
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## Intended use
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Research inspection of single-chain, all-heavy-atom protein structures of at most 256 residues:
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draw independent samples of where MarS-FM-style flow matching places the backbone after the
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trained lag, and compare against source MarS-FM. Each draw is an independent sample, not a frame
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of a trajectory. Do not use Senba for clinical, diagnostic, or design decisions, and do not
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present its outputs as physical-time dynamics, kinetics, or equilibrium ensembles beyond the
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retention evidence above.
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## How to run
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| 135 |
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```bash
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git clone https://github.com/valence-labs/mars-fm.git && cd mars-fm
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git checkout 4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946
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pip install "torch>=2.5" "pytorch-lightning>=2.4" torchdiffeq "numpy<2" \
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dm-tree fair-esm biopython pandas scipy
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hf download pikachuandme1/senba senba.ckpt inference_example.py --local-dir senba
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PYTHONPATH=. python senba/inference_example.py \
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--pdb 1ubq.pdb --chain A \
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--checkpoint senba/senba.ckpt \
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--expect-sha256 f02dcf6a97848c834e3c0be7d848c1068d1d0eb7976d8d6bcfbc98d4114e9c7c \
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--samples 8 --ode-steps 10 --seed 20260904 \
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--out senba-1ubq.pdb
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```
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The script writes a multi-model PDB: MODEL 1 is the input, MODELS 2 to K+1 are K independent
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draws. It refuses structures with missing heavy atoms, non-standard residues, or several chains
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rather than silently zero-filling, and warns when the input exceeds the validated 256 residues.
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A GPU is recommended; CPU works but is slow.
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+
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To load the checkpoint yourself, follow `inference_example.py`: build the same batch layout as
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MarS-FM (`torsions`, `torsion_mask`, `trans`, `rots`, `seqres`, `mask`), then call
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`MarSModule.inference(batch, num_steps=10)`.
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| 159 |
+
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## Files
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| 161 |
+
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| 162 |
+
| Path | Contents |
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| 163 |
+
| --- | --- |
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| 164 |
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| `senba.ckpt` | The selected checkpoint, byte-identical to the receipt hash |
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| `inference_example.py` | Sampling script against the pinned MarS-FM source |
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| 166 |
+
| `receipts/selection-v2.json` | Selection receipt (`dynaview-mars-fm-epoch-sweep-selection-v2`) |
|
| 167 |
+
| `receipts/interpolation-config.json`, `receipts/interpolation-result.json` | Anchoring receipt for the selected checkpoint |
|
| 168 |
+
| `receipts/parent/training-config.json`, `receipts/parent/training-result.json` | Seed-1 parent fine-tune receipt with per-epoch validation losses |
|
| 169 |
+
| `receipts/full-transition-comparison.json` | 28-domain transition comparison vs source and persistence |
|
| 170 |
+
| `receipts/head-to-head-vs-previous-senba.json` | 28-domain comparison vs the previous Senba checkpoint |
|
| 171 |
+
| `receipts/equilibrium-suite-comparison.json` | Seven-observable retention suite with per-domain rows |
|
| 172 |
+
| `receipts/replications/seed2/`, `receipts/replications/seed3/` | Seed-2 and seed-3 parent, anchoring, and compact-panel receipts |
|
| 173 |
+
| `protocols/` | The four preregistered protocols, frozen before the outputs they govern existed |
|
| 174 |
+
| `release-manifest.json` | SHA-256 of every published file |
|
| 175 |
+
|
| 176 |
+
## Compute
|
| 177 |
+
|
| 178 |
+
The three ten-epoch parents took 378.21 H100-seconds in aggregate (121.80, 126.07 mean). Observed
|
| 179 |
+
Modal billing for the whole 2026-08-25 search and validation campaign was $19.45 ($10.60
|
| 180 |
+
adaptation, $8.85 validation), including rejected, interrupted, and long-epoch runs; that is not
|
| 181 |
+
the cost of the selected two-minute training run alone.
|
| 182 |
+
|
| 183 |
+
## License and attribution
|
| 184 |
+
|
| 185 |
+
Weights and code: MIT (see `LICENSE`). MarS-FM source model and code are MIT, Copyright (c) 2026
|
| 186 |
+
Valence Labs. The adaptation data, mdCATH, is CC BY 4.0; attribute it when you use these weights.
|
| 187 |
+
|
| 188 |
+
## Citation
|
| 189 |
+
|
| 190 |
+
If you use Senba, cite MarS-FM and mdCATH:
|
| 191 |
+
|
| 192 |
+
```bibtex
|
| 193 |
+
@inproceedings{marsfm2026,
|
| 194 |
+
title = {MarS-FM: Generative Modeling of Molecular Dynamics via Markov State Models},
|
| 195 |
+
booktitle = {International Conference on Learning Representations (ICLR)},
|
| 196 |
+
year = {2026},
|
| 197 |
+
note = {arXiv:2509.24779}
|
| 198 |
+
}
|
| 199 |
+
|
| 200 |
+
@article{mdcath2024,
|
| 201 |
+
title = {mdCATH: A Large-Scale MD Dataset for Data-Driven Computational Biophysics},
|
| 202 |
+
journal = {arXiv preprint arXiv:2407.14794},
|
| 203 |
+
year = {2024}
|
| 204 |
+
}
|
| 205 |
+
```
|
| 206 |
+
|
| 207 |
+
Senba itself: Paper Crane, "Senba: a source-anchored MarS-FM adaptation for mdCATH transitions,"
|
| 208 |
+
model release, 2026, <https://huggingface.co/pikachuandme1/senba>.
|
inference_example.py
ADDED
|
@@ -0,0 +1,186 @@
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|
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|
|
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|
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|
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|
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|
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|
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|
|
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|
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|
|
|
|
|
|
|
|
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|
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|
|
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|
|
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|
|
|
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|
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|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
#!/usr/bin/env python
|
| 2 |
+
"""Sample Senba (adapted MarS-FM) transition endpoints for one protein structure.
|
| 3 |
+
|
| 4 |
+
Senba is a MarS-FM checkpoint, so it loads with the pinned MarS-FM source
|
| 5 |
+
(https://github.com/valence-labs/mars-fm at 4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946).
|
| 6 |
+
Put that repository on PYTHONPATH, then run:
|
| 7 |
+
|
| 8 |
+
python inference_example.py --pdb 1ubq.pdb --chain A \
|
| 9 |
+
--checkpoint senba.ckpt \
|
| 10 |
+
--expect-sha256 f02dcf6a97848c834e3c0be7d848c1068d1d0eb7976d8d6bcfbc98d4114e9c7c \
|
| 11 |
+
--samples 8 --ode-steps 10 --seed 20260904 --out senba-1ubq.pdb
|
| 12 |
+
|
| 13 |
+
What you get: a multi-model PDB whose MODEL 1 is the input heavy-atom structure
|
| 14 |
+
and whose MODELS 2..K+1 are K independent samples of where the model places the
|
| 15 |
+
chain after the trained lag (50 mdCATH frames at 450 K). The samples are not a
|
| 16 |
+
trajectory, carry no physical clock, and were validated only on single-chain
|
| 17 |
+
mdCATH domains of at most 256 residues. Every claim about Senba is bounded to
|
| 18 |
+
that validation evidence; see README.md.
|
| 19 |
+
|
| 20 |
+
Input requirements: one protein chain, standard amino acids only, every heavy
|
| 21 |
+
atom present (crystal structures with truncated side chains are rejected rather
|
| 22 |
+
than silently zero-filled). HETATM records, hydrogens, alternate locations other
|
| 23 |
+
than A, and other chains are dropped before parsing.
|
| 24 |
+
"""
|
| 25 |
+
|
| 26 |
+
from __future__ import annotations
|
| 27 |
+
|
| 28 |
+
import argparse
|
| 29 |
+
import hashlib
|
| 30 |
+
import sys
|
| 31 |
+
from pathlib import Path
|
| 32 |
+
|
| 33 |
+
import numpy as np
|
| 34 |
+
import torch
|
| 35 |
+
|
| 36 |
+
torch.serialization.add_safe_globals([argparse.Namespace])
|
| 37 |
+
|
| 38 |
+
from mars.data.geometry import atom14_to_atom37, atom14_to_frames, atom37_to_torsions # noqa: E402
|
| 39 |
+
from mars.model.module import MarSModule # noqa: E402
|
| 40 |
+
from mars.utils import atom14_to_pdb # noqa: E402
|
| 41 |
+
from mars.vendored.openfold import protein # noqa: E402
|
| 42 |
+
from mars.vendored.openfold import residue_constants as rc # noqa: E402
|
| 43 |
+
|
| 44 |
+
VALIDATED_MAX_RESIDUES = 256
|
| 45 |
+
TRAINED_LAG_FRAMES = 50
|
| 46 |
+
TRAINED_TEMPERATURE_K = 450
|
| 47 |
+
|
| 48 |
+
|
| 49 |
+
def sha256_file(path: Path) -> str:
|
| 50 |
+
digest = hashlib.sha256()
|
| 51 |
+
with path.open("rb") as handle:
|
| 52 |
+
while chunk := handle.read(8 * 1024 * 1024):
|
| 53 |
+
digest.update(chunk)
|
| 54 |
+
return digest.hexdigest()
|
| 55 |
+
|
| 56 |
+
|
| 57 |
+
def clean_pdb_text(pdb_text: str, chain_id: str | None) -> str:
|
| 58 |
+
"""Keep ATOM records of one chain with primary alternate locations only."""
|
| 59 |
+
kept: list[str] = []
|
| 60 |
+
for line in pdb_text.splitlines():
|
| 61 |
+
if not line.startswith("ATOM "):
|
| 62 |
+
continue
|
| 63 |
+
if len(line) < 54:
|
| 64 |
+
raise ValueError("truncated ATOM record in input PDB")
|
| 65 |
+
if line[16] not in (" ", "A"):
|
| 66 |
+
continue
|
| 67 |
+
if chain_id is not None and line[21].strip() != chain_id:
|
| 68 |
+
continue
|
| 69 |
+
kept.append(line[:16] + " " + line[17:])
|
| 70 |
+
if not kept:
|
| 71 |
+
raise ValueError("no ATOM records matched the requested chain")
|
| 72 |
+
return "\n".join(kept) + "\nEND\n"
|
| 73 |
+
|
| 74 |
+
|
| 75 |
+
def pdb_to_atom14(pdb_text: str, chain_id: str | None) -> tuple[np.ndarray, str]:
|
| 76 |
+
prot = protein.from_pdb_string(clean_pdb_text(pdb_text, chain_id))
|
| 77 |
+
if prot.chain_index is not None and len(np.unique(prot.chain_index)) != 1:
|
| 78 |
+
raise ValueError("the structure has several chains; pass --chain")
|
| 79 |
+
if prot.aatype.size == 0:
|
| 80 |
+
raise ValueError("no residues were parsed")
|
| 81 |
+
if np.any(prot.aatype >= rc.restype_num):
|
| 82 |
+
raise ValueError("non-standard residues are not supported by MarS-FM")
|
| 83 |
+
n_res = int(prot.aatype.shape[0])
|
| 84 |
+
atom14 = np.zeros((n_res, 14, 3), dtype=np.float32)
|
| 85 |
+
for index, aatype in enumerate(prot.aatype.tolist()):
|
| 86 |
+
names = rc.restype_name_to_atom14_names[rc.restype_1to3[rc.restypes[aatype]]]
|
| 87 |
+
for slot, name in enumerate(names):
|
| 88 |
+
if not name:
|
| 89 |
+
continue
|
| 90 |
+
atom_index = rc.atom_order[name]
|
| 91 |
+
if prot.atom_mask[index, atom_index] <= 0:
|
| 92 |
+
raise ValueError(
|
| 93 |
+
f"residue {index + 1} ({rc.restypes[aatype]}) is missing heavy atom {name}; "
|
| 94 |
+
"supply a structure with complete side chains"
|
| 95 |
+
)
|
| 96 |
+
atom14[index, slot] = prot.atom_positions[index, atom_index]
|
| 97 |
+
sequence = "".join(rc.restypes[aatype] for aatype in prot.aatype.tolist())
|
| 98 |
+
return atom14, sequence
|
| 99 |
+
|
| 100 |
+
|
| 101 |
+
def build_batch(atom14: np.ndarray, sequence: str, samples: int, device: torch.device) -> dict:
|
| 102 |
+
"""Mirror the batch layout used by the frozen Senba validation runs."""
|
| 103 |
+
seqres = torch.tensor([rc.restype_order[residue] for residue in sequence])
|
| 104 |
+
seqres = seqres.unsqueeze(0).repeat(samples, 1)
|
| 105 |
+
repeated = np.repeat(atom14[None], samples, axis=0).astype(np.float32, copy=False)
|
| 106 |
+
frames = atom14_to_frames(torch.from_numpy(repeated))
|
| 107 |
+
atom37 = torch.from_numpy(atom14_to_atom37(repeated, seqres)).float()
|
| 108 |
+
torsions, torsion_mask = atom37_to_torsions(atom37, seqres)
|
| 109 |
+
batch = {
|
| 110 |
+
"torsions": torsions.unsqueeze(1),
|
| 111 |
+
"torsion_mask": torsion_mask,
|
| 112 |
+
"trans": frames._trans.unsqueeze(1),
|
| 113 |
+
"rots": frames._rots._rot_mats.unsqueeze(1),
|
| 114 |
+
"seqres": seqres,
|
| 115 |
+
"mask": torch.ones_like(seqres, dtype=torch.float32),
|
| 116 |
+
}
|
| 117 |
+
return {key: value.to(device) for key, value in batch.items()}
|
| 118 |
+
|
| 119 |
+
|
| 120 |
+
def kabsch_rmsd(reference: np.ndarray, mobile: np.ndarray) -> float:
|
| 121 |
+
"""C-alpha RMSD after optimal superposition (no reflection)."""
|
| 122 |
+
ref = reference - reference.mean(axis=0)
|
| 123 |
+
mob = mobile - mobile.mean(axis=0)
|
| 124 |
+
covariance = mob.T @ ref
|
| 125 |
+
u, _, vt = np.linalg.svd(covariance)
|
| 126 |
+
sign = np.sign(np.linalg.det(u @ vt))
|
| 127 |
+
correction = np.diag([1.0, 1.0, sign])
|
| 128 |
+
rotation = u @ correction @ vt
|
| 129 |
+
aligned = mob @ rotation
|
| 130 |
+
return float(np.sqrt(np.mean(np.sum((aligned - ref) ** 2, axis=1))))
|
| 131 |
+
|
| 132 |
+
|
| 133 |
+
def main() -> int:
|
| 134 |
+
parser = argparse.ArgumentParser(description=__doc__, formatter_class=argparse.RawDescriptionHelpFormatter)
|
| 135 |
+
parser.add_argument("--pdb", required=True, type=Path, help="input PDB file (heavy atoms, one chain)")
|
| 136 |
+
parser.add_argument("--chain", default=None, help="chain identifier to use when the file has several")
|
| 137 |
+
parser.add_argument("--checkpoint", required=True, type=Path, help="path to senba.ckpt")
|
| 138 |
+
parser.add_argument("--expect-sha256", default=None, help="refuse to run unless the checkpoint hash matches")
|
| 139 |
+
parser.add_argument("--samples", type=int, default=8, help="independent endpoint draws")
|
| 140 |
+
parser.add_argument("--ode-steps", type=int, default=10, help="flow ODE steps (validation used 10)")
|
| 141 |
+
parser.add_argument("--seed", type=int, default=0)
|
| 142 |
+
parser.add_argument("--out", required=True, type=Path, help="multi-model PDB to write")
|
| 143 |
+
parser.add_argument("--device", default="cuda" if torch.cuda.is_available() else "cpu")
|
| 144 |
+
args = parser.parse_args()
|
| 145 |
+
|
| 146 |
+
if args.samples < 1 or args.ode_steps < 1:
|
| 147 |
+
parser.error("--samples and --ode-steps must be positive")
|
| 148 |
+
digest = sha256_file(args.checkpoint)
|
| 149 |
+
if args.expect_sha256 is not None and digest != args.expect_sha256.lower().removeprefix("sha256:"):
|
| 150 |
+
print(f"checkpoint hash {digest} does not match --expect-sha256", file=sys.stderr)
|
| 151 |
+
return 2
|
| 152 |
+
|
| 153 |
+
atom14, sequence = pdb_to_atom14(args.pdb.read_text(), args.chain)
|
| 154 |
+
if len(sequence) > VALIDATED_MAX_RESIDUES:
|
| 155 |
+
print(
|
| 156 |
+
f"warning: {len(sequence)} residues exceeds the validated scope of "
|
| 157 |
+
f"{VALIDATED_MAX_RESIDUES}; outputs are outside the published evidence",
|
| 158 |
+
file=sys.stderr,
|
| 159 |
+
)
|
| 160 |
+
|
| 161 |
+
device = torch.device(args.device)
|
| 162 |
+
torch.manual_seed(args.seed)
|
| 163 |
+
if device.type == "cuda":
|
| 164 |
+
torch.cuda.manual_seed_all(args.seed)
|
| 165 |
+
model = MarSModule.load_from_checkpoint(str(args.checkpoint), map_location="cpu")
|
| 166 |
+
model.eval().to(device)
|
| 167 |
+
batch = build_batch(atom14, sequence, args.samples, device)
|
| 168 |
+
with torch.no_grad():
|
| 169 |
+
generated_atom14, _ = model.inference(batch, num_steps=args.ode_steps)
|
| 170 |
+
samples = generated_atom14[:, 0].float().cpu().numpy() # [K, L, 14, 3]
|
| 171 |
+
|
| 172 |
+
aatype = np.array([rc.restype_order[residue] for residue in sequence])
|
| 173 |
+
atom14_to_pdb(np.concatenate([atom14[None], samples], axis=0), aatype, str(args.out))
|
| 174 |
+
|
| 175 |
+
reference_ca = atom14[:, 1]
|
| 176 |
+
rmsds = [kabsch_rmsd(reference_ca, sample[:, 1]) for sample in samples]
|
| 177 |
+
print(f"checkpoint sha256 {digest}")
|
| 178 |
+
print(f"sequence length {len(sequence)}; lag {TRAINED_LAG_FRAMES} frames at {TRAINED_TEMPERATURE_K} K")
|
| 179 |
+
print(f"wrote {args.out} with MODEL 1 = input and MODELS 2..{args.samples + 1} = independent draws")
|
| 180 |
+
print("aligned C-alpha RMSD of each draw from the input (A): " + ", ".join(f"{value:.3f}" for value in rmsds))
|
| 181 |
+
print("these draws are independent samples at one lag, not a trajectory or a physical-time prediction")
|
| 182 |
+
return 0
|
| 183 |
+
|
| 184 |
+
|
| 185 |
+
if __name__ == "__main__":
|
| 186 |
+
sys.exit(main())
|
protocols/MARS_FM_ANCHOR08_FULL_VALIDATION_V1_PROTOCOL.md
ADDED
|
@@ -0,0 +1,125 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
# MarS-FM Anchor08 complete eligible validation protocol
|
| 2 |
+
|
| 3 |
+
Status: frozen validation-stage protocol; no test, final-model, commercial,
|
| 4 |
+
state-of-the-art, or field-changing claim.
|
| 5 |
+
|
| 6 |
+
Frozen on 2026-08-02 after the seed-1 Anchor08 candidate passed the previously
|
| 7 |
+
frozen eight-protein transition and equilibrium-retention suites, but before
|
| 8 |
+
generating or inspecting exact-lag outputs for the remaining twenty eligible
|
| 9 |
+
validation proteins.
|
| 10 |
+
|
| 11 |
+
## Scientific question
|
| 12 |
+
|
| 13 |
+
Does the small exact-lag transition gain of the frozen seed-1 Anchor08
|
| 14 |
+
checkpoint survive the complete sequence-length-eligible validation population
|
| 15 |
+
without changing the checkpoint, inference settings, metrics, or population?
|
| 16 |
+
|
| 17 |
+
This is a candidate-qualification experiment. A pass does not establish
|
| 18 |
+
physical kinetics, broad sequence generalization, field leadership, or test
|
| 19 |
+
performance.
|
| 20 |
+
|
| 21 |
+
## Immutable identities
|
| 22 |
+
|
| 23 |
+
- Standard mdCATH manifest:
|
| 24 |
+
`sha256:53e81a90c0dcf3e00a814744f62d25db52f5aa8790475294dac451d36d728b8b`.
|
| 25 |
+
- Development subset manifest:
|
| 26 |
+
`sha256:163ab0043d86b5a2731e1b1a233af27fb069049897d657fd5c39bd54b1343b3f`.
|
| 27 |
+
- Source MarS-FM checkpoint:
|
| 28 |
+
`sha256:f56794cc5d1a8e5263031944f932384dd785fe945553612fe76fe1e9191fa879`.
|
| 29 |
+
- Candidate run:
|
| 30 |
+
`mars-fm-mdcath-anchor08-exactlag-128x32-20260801-s1-v1`.
|
| 31 |
+
- Candidate checkpoint:
|
| 32 |
+
`sha256:802042f2d5c1aa8adf07a9a935063ed970aa38fdfba1993b236cb0364c9a0fae`.
|
| 33 |
+
- MarS-FM source revision:
|
| 34 |
+
`4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946`.
|
| 35 |
+
- Standard test records opened: zero.
|
| 36 |
+
|
| 37 |
+
## Complete eligible population
|
| 38 |
+
|
| 39 |
+
Use every validation record in frozen manifest order whose sequence length is
|
| 40 |
+
at most the pinned MarS-FM crop of 256 residues. No eligible protein may be
|
| 41 |
+
removed after evaluation starts:
|
| 42 |
+
|
| 43 |
+
1. `1e7uA04` (158)
|
| 44 |
+
2. `1rquA01` (52)
|
| 45 |
+
3. `1q16B03` (77)
|
| 46 |
+
4. `1d1rA00` (83)
|
| 47 |
+
5. `2k4qA00` (156)
|
| 48 |
+
6. `2f2cA02` (106)
|
| 49 |
+
7. `5k2mA01` (96)
|
| 50 |
+
8. `2dp9A01` (100)
|
| 51 |
+
9. `1nktA02` (122)
|
| 52 |
+
10. `3mg3A01` (147)
|
| 53 |
+
11. `2incC00` (83)
|
| 54 |
+
12. `4nreA01` (120)
|
| 55 |
+
13. `1h4yA00` (115)
|
| 56 |
+
14. `2kjrA01` (80)
|
| 57 |
+
15. `4qncB00` (82)
|
| 58 |
+
16. `3aekA03` (123)
|
| 59 |
+
17. `2ji7A03` (212)
|
| 60 |
+
18. `3i01A03` (228)
|
| 61 |
+
19. `2izwC00` (208)
|
| 62 |
+
20. `2k54A00` (123)
|
| 63 |
+
21. `4pkiG02` (171)
|
| 64 |
+
22. `4b96A00` (151)
|
| 65 |
+
23. `4deqA02` (53)
|
| 66 |
+
24. `3pt1A02` (120)
|
| 67 |
+
25. `3atsA01` (116)
|
| 68 |
+
26. `3d8lA00` (91)
|
| 69 |
+
27. `3tdgA01` (66)
|
| 70 |
+
28. `1jeyB03` (102)
|
| 71 |
+
|
| 72 |
+
The first eight existing receipts may be reused only after their settings,
|
| 73 |
+
checkpoint identities, source transitions, and hashes pass the same aggregator
|
| 74 |
+
validation as newly generated receipts.
|
| 75 |
+
|
| 76 |
+
## Frozen transition and inference settings
|
| 77 |
+
|
| 78 |
+
- Role: validation only.
|
| 79 |
+
- Temperature: 450 K.
|
| 80 |
+
- Replicas: all five available replicas.
|
| 81 |
+
- Starts per replica: four deterministic evenly spaced starts.
|
| 82 |
+
- Transition lag: exactly 50 source frames within one replica.
|
| 83 |
+
- Stochastic samples per start: four.
|
| 84 |
+
- ODE steps per sample: ten.
|
| 85 |
+
- Inference seed: `20260801` for both source and candidate.
|
| 86 |
+
- Alignment and C-alpha metric implementation: unchanged from
|
| 87 |
+
`dynaview-mars-fm-exact-lag-validation-v1`.
|
| 88 |
+
- Bootstrap unit: protein.
|
| 89 |
+
- Bootstrap resamples: 100,000.
|
| 90 |
+
- Bootstrap seed: `20260801`.
|
| 91 |
+
|
| 92 |
+
Best-of-four error is diagnostic only because selecting a sample using the
|
| 93 |
+
unknown future is not an inference-time capability. The primary score is the
|
| 94 |
+
ensemble-mean endpoint C-alpha RMSD.
|
| 95 |
+
|
| 96 |
+
## Frozen advancement gate
|
| 97 |
+
|
| 98 |
+
Anchor08 advances to multi-lag and kinetic validation only if all conditions
|
| 99 |
+
hold across the complete 28-protein population:
|
| 100 |
+
|
| 101 |
+
1. mean ensemble-endpoint RMSD improvement over source MarS-FM is positive and
|
| 102 |
+
its protein-bootstrap 95% interval excludes zero;
|
| 103 |
+
2. at least 75% of proteins improve over source MarS-FM;
|
| 104 |
+
3. mean ensemble-endpoint RMSD improvement over coordinate persistence is
|
| 105 |
+
positive and its protein-bootstrap 95% interval excludes zero;
|
| 106 |
+
4. at least 75% of proteins improve over coordinate persistence;
|
| 107 |
+
5. no source or candidate receipt uses a test record, crosses replicas, changes
|
| 108 |
+
the lag, or disagrees on the exact transition population;
|
| 109 |
+
6. the candidate checkpoint and every receipt retain the immutable identities
|
| 110 |
+
above.
|
| 111 |
+
|
| 112 |
+
No minimum practical effect size is inferred from this experiment. Even a pass
|
| 113 |
+
only establishes broad validation nonregression/improvement at one lag. The
|
| 114 |
+
later field-competitiveness gate must preregister a practically meaningful
|
| 115 |
+
effect threshold before matched competitor outputs are inspected.
|
| 116 |
+
|
| 117 |
+
## Failure and continuation policy
|
| 118 |
+
|
| 119 |
+
If any advancement condition fails, do not open standard test data and do not
|
| 120 |
+
delete proteins, change inference seeds, or relax the gate. Diagnose failures
|
| 121 |
+
on train/validation data under a fresh run identity. If the gate passes, freeze
|
| 122 |
+
the result and design the multi-lag, replica-noise, semigroup/kinetic, and
|
| 123 |
+
matched-competitor protocols before generating those outputs.
|
| 124 |
+
|
| 125 |
+
All generated arrays and receipts remain validation-only development evidence.
|
protocols/MARS_FM_EPOCH_SWEEP_V1_PROTOCOL.md
ADDED
|
@@ -0,0 +1,108 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
# MarS-FM exact-lag epoch-sweep v1 development protocol
|
| 2 |
+
|
| 3 |
+
Status: frozen development sweep; no test, final-model, state-of-the-art, or
|
| 4 |
+
commercial claim.
|
| 5 |
+
|
| 6 |
+
Frozen on 2026-08-25 before launching any run in this sweep or inspecting any
|
| 7 |
+
new candidate output.
|
| 8 |
+
|
| 9 |
+
## Question
|
| 10 |
+
|
| 11 |
+
The existing five-epoch exact-lag parent ended with validation loss still
|
| 12 |
+
decreasing. This sweep asks whether a longer exact-lag fine-tune, followed by
|
| 13 |
+
source-weight anchoring, produces a larger endpoint improvement without
|
| 14 |
+
damaging the source model's equilibrium ensemble.
|
| 15 |
+
|
| 16 |
+
This is a retrospective development study. The 128-train/32-validation subset
|
| 17 |
+
and the 28 sequence-length-eligible validation proteins were used by the prior
|
| 18 |
+
Anchor08 program. Results from this sweep cannot be described as pristine
|
| 19 |
+
validation. The 495-record standard test partition remains unopened.
|
| 20 |
+
|
| 21 |
+
## Fixed training contract
|
| 22 |
+
|
| 23 |
+
Every parent starts from the same pinned public MarS-FM checkpoint and changes
|
| 24 |
+
only the epoch budget.
|
| 25 |
+
|
| 26 |
+
- Source checkpoint SHA-256:
|
| 27 |
+
`f56794cc5d1a8e5263031944f932384dd785fe945553612fe76fe1e9191fa879`.
|
| 28 |
+
- MarS-FM source revision:
|
| 29 |
+
`4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946`.
|
| 30 |
+
- Development subset semantic SHA-256:
|
| 31 |
+
`163ab0043d86b5a2731e1b1a233af27fb069049897d657fd5c39bd54b1343b3f`.
|
| 32 |
+
- Roles: 128 train domains and 32 validation domains, with no test records.
|
| 33 |
+
- Temperature: 450 K.
|
| 34 |
+
- Objective: observed same-replica pairs separated by exactly 50 frames.
|
| 35 |
+
- Trainable scope: all 34,152,521 parameters.
|
| 36 |
+
- Optimizer: fresh Adam state from the public checkpoint.
|
| 37 |
+
- Learning rate: `3e-6`.
|
| 38 |
+
- Batch size: 8.
|
| 39 |
+
- Seed: `20260825`.
|
| 40 |
+
- Validation population and flow randomness: fixed and replayed.
|
| 41 |
+
- Epoch budgets: `[5, 10, 20, 40, 80, 160]`.
|
| 42 |
+
|
| 43 |
+
Each epoch contains 16 optimizer steps, so the parent budgets contain
|
| 44 |
+
`[80, 160, 320, 640, 1280, 2560]` optimizer steps.
|
| 45 |
+
|
| 46 |
+
## Source-anchor grid
|
| 47 |
+
|
| 48 |
+
Longer parents can move farther from the source checkpoint, so a fixed
|
| 49 |
+
interpolation coefficient would confound training length with update size.
|
| 50 |
+
Each parent is therefore interpolated at four coefficients chosen so that the
|
| 51 |
+
heuristic product `epochs * alpha` is one of `[0.20, 0.30, 0.40, 0.60]`.
|
| 52 |
+
This product is a grid-design device, not a physical quantity or an assumption
|
| 53 |
+
that weight displacement is linear in epochs.
|
| 54 |
+
|
| 55 |
+
| Epochs | Interpolation coefficients |
|
| 56 |
+
| ---: | --- |
|
| 57 |
+
| 5 | `0.04`, `0.06`, `0.08`, `0.12` |
|
| 58 |
+
| 10 | `0.02`, `0.03`, `0.04`, `0.06` |
|
| 59 |
+
| 20 | `0.01`, `0.015`, `0.02`, `0.03` |
|
| 60 |
+
| 40 | `0.005`, `0.0075`, `0.01`, `0.015` |
|
| 61 |
+
| 80 | `0.0025`, `0.00375`, `0.005`, `0.0075` |
|
| 62 |
+
| 160 | `0.00125`, `0.001875`, `0.0025`, `0.00375` |
|
| 63 |
+
|
| 64 |
+
All 24 interpolated checkpoints must be created and screened. A missing or
|
| 65 |
+
failed run is reported, not silently replaced.
|
| 66 |
+
|
| 67 |
+
## Development screen
|
| 68 |
+
|
| 69 |
+
The source and every candidate use the same compact eight-protein panel, all
|
| 70 |
+
five replicas, four fixed starts per replica, four samples per start, exact lag
|
| 71 |
+
50, ten ODE steps, and inference seed `20260825`. Proteins are the bootstrap
|
| 72 |
+
unit with 100,000 resamples and bootstrap seed `20260825`.
|
| 73 |
+
|
| 74 |
+
A candidate remains eligible only if:
|
| 75 |
+
|
| 76 |
+
1. its parent improves the fixed paired validation loss over the source;
|
| 77 |
+
2. its mean ensemble-endpoint RMSD improvement over source is positive with a
|
| 78 |
+
95% protein-bootstrap interval above zero;
|
| 79 |
+
3. at least six of eight proteins improve over source;
|
| 80 |
+
4. its mean improvement over coordinate persistence is positive; and
|
| 81 |
+
5. it passes all seven existing equilibrium-retention limits on the fixed
|
| 82 |
+
`1e7uA04` pilot using breadth 200, 500 retained samples, 50 ODE steps, and
|
| 83 |
+
seed `20260825`.
|
| 84 |
+
|
| 85 |
+
Among eligible candidates, select the largest mean ensemble-endpoint RMSD
|
| 86 |
+
improvement over source. An exact tie is broken by fewer epochs, then by the
|
| 87 |
+
smaller interpolation coefficient.
|
| 88 |
+
|
| 89 |
+
If the selected candidate uses 160 epochs, the epoch boundary is unresolved.
|
| 90 |
+
Extend the parent grid to 320 and 640 epochs with the same four heuristic
|
| 91 |
+
products before selecting a final configuration. Otherwise do not extend the
|
| 92 |
+
grid after observing results.
|
| 93 |
+
|
| 94 |
+
## Qualification after selection
|
| 95 |
+
|
| 96 |
+
Freeze the selected epoch count, interpolation coefficient, checkpoint,
|
| 97 |
+
inference settings, and selection receipt before further evaluation. Then:
|
| 98 |
+
|
| 99 |
+
1. run the selected seed-1 candidate on all 28 eligible validation proteins;
|
| 100 |
+
2. repeat the exact training and interpolation configuration with seeds
|
| 101 |
+
`20260826` and `20260827` and run the compact transition panel;
|
| 102 |
+
3. run the existing eight-protein equilibrium-retention aggregate for the
|
| 103 |
+
selected seed-1 checkpoint; and
|
| 104 |
+
4. leave the standard test partition unopened.
|
| 105 |
+
|
| 106 |
+
These qualification results remain development evidence because the
|
| 107 |
+
validation population was previously inspected. Any new external or test
|
| 108 |
+
claim requires a separately frozen untouched evaluation boundary.
|
protocols/MARS_FM_EQUILIBRIUM_SUITE_PROTOCOL.md
ADDED
|
@@ -0,0 +1,37 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
# MarS-FM equilibrium-suite validation protocol
|
| 2 |
+
|
| 3 |
+
Status: frozen validation-stage protocol; no final-model or state-of-the-art
|
| 4 |
+
claim.
|
| 5 |
+
|
| 6 |
+
Frozen on 2026-07-31 after anchor08 passed the designated one-protein pilot,
|
| 7 |
+
but before generating source or anchor08 equilibrium outputs for the other
|
| 8 |
+
seven proteins.
|
| 9 |
+
|
| 10 |
+
## Population and generation
|
| 11 |
+
|
| 12 |
+
Use the first eight validation domains in the frozen 128x32 manifest whose
|
| 13 |
+
sequence length is at most the pinned model crop of 256 residues:
|
| 14 |
+
`1e7uA04`, `1rquA01`, `1q16B03`, `1d1rA00`, `2k4qA00`, `2f2cA02`,
|
| 15 |
+
`5k2mA01`, and `2dp9A01`.
|
| 16 |
+
|
| 17 |
+
For both pinned source MarS-FM and the seed-1 anchor08 candidate, generate the
|
| 18 |
+
official breadth-first tree with 200 children per call, 500 retained samples,
|
| 19 |
+
chunk size 100, 50 ODE steps, and seed `20260731`. Score against all five
|
| 20 |
+
450 K replicas with the existing all-C-alpha aligned equilibrium metrics.
|
| 21 |
+
|
| 22 |
+
## Protein-level retention gate
|
| 23 |
+
|
| 24 |
+
For each metric, define degradation in its unfavorable direction and use
|
| 25 |
+
proteins as the paired bootstrap unit with 100,000 resamples and seed
|
| 26 |
+
`20260801`. A metric passes only if:
|
| 27 |
+
|
| 28 |
+
1. the upper endpoint of its 95% bootstrap interval for mean degradation is
|
| 29 |
+
no greater than the frozen per-protein pilot limit;
|
| 30 |
+
2. at least 75% of proteins individually remain within that limit; and
|
| 31 |
+
3. no protein degrades by more than twice that limit.
|
| 32 |
+
|
| 33 |
+
All seven metrics and their limits are inherited unchanged from
|
| 34 |
+
`MARS_FM_HYBRID_V1_PROTOCOL.md`. Every metric must pass. This is an internal
|
| 35 |
+
retention gate, not an equivalence test or evidence of field leadership.
|
| 36 |
+
|
| 37 |
+
Standard mdCATH test records remain unopened.
|
protocols/MARS_FM_MDCATH_ADAPTATION_PROTOCOL.md
ADDED
|
@@ -0,0 +1,88 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| 1 |
+
# MarS-FM mdCATH adaptation protocol
|
| 2 |
+
|
| 3 |
+
Status: frozen development protocol; no final-model or state-of-the-art claim.
|
| 4 |
+
|
| 5 |
+
Frozen on 2026-07-31 before inspecting the first adapted checkpoint's
|
| 6 |
+
structural or exact-lag benchmark outputs.
|
| 7 |
+
|
| 8 |
+
## Scientific question
|
| 9 |
+
|
| 10 |
+
Can the pinned public MarS-FM checkpoint be adapted on the standard mdCATH
|
| 11 |
+
training split so that it preserves its strong equilibrium-ensemble behavior
|
| 12 |
+
while becoming a useful predictor of observed, same-replica lagged
|
| 13 |
+
transitions?
|
| 14 |
+
|
| 15 |
+
The two development objectives are separate:
|
| 16 |
+
|
| 17 |
+
- `msm`: reproduce MarS-FM's state-balanced transition sampling;
|
| 18 |
+
- `exact_lag`: use observed `(t, t + 50 frames)` pairs from one replica, with
|
| 19 |
+
starting-state cluster balancing and no replica crossing.
|
| 20 |
+
|
| 21 |
+
The exact-lag objective is a DynaView development contribution. It is not a
|
| 22 |
+
validated kinetic model unless it passes the kinetic gates below.
|
| 23 |
+
|
| 24 |
+
## Frozen identities and data boundary
|
| 25 |
+
|
| 26 |
+
- MarS-FM source code commit:
|
| 27 |
+
`4fc17d86cd7e22dda6353f2f1f6bf4b40c9ce946`.
|
| 28 |
+
- MarS-FM model revision:
|
| 29 |
+
`1e957cd4b9f1a054ceb0c2104f40ba6f3cc0d8d0`.
|
| 30 |
+
- Source checkpoint SHA-256:
|
| 31 |
+
`f56794cc5d1a8e5263031944f932384dd785fe945553612fe76fe1e9191fa879`.
|
| 32 |
+
- Standard split semantic SHA-256:
|
| 33 |
+
`53e81a90c0dcf3e00a814744f62d25db52f5aa8790475294dac451d36d728b8b`.
|
| 34 |
+
- Development subset semantic SHA-256:
|
| 35 |
+
`163ab0043d86b5a2731e1b1a233af27fb069049897d657fd5c39bd54b1343b3f`.
|
| 36 |
+
- Development subset: 128 train and 32 validation domains, all five 450 K
|
| 37 |
+
replicas, with byte-bound source and converted-array receipts.
|
| 38 |
+
- Standard test records opened during adaptation and selection: zero.
|
| 39 |
+
|
| 40 |
+
All validation transition items are materialized once. MarS-FM's stochastic
|
| 41 |
+
flow noise and interpolation times are replayed from a dedicated validation
|
| 42 |
+
seed, and the caller's training RNG state is restored afterward. Source loss
|
| 43 |
+
is evaluated twice and must replay within `1e-6` before a run is valid.
|
| 44 |
+
|
| 45 |
+
## Development scorecard
|
| 46 |
+
|
| 47 |
+
### Transport-loss gate
|
| 48 |
+
|
| 49 |
+
A checkpoint may enter molecular benchmarking only if its best loss is lower
|
| 50 |
+
than the untouched source model on the identical validation transitions and
|
| 51 |
+
identical flow randomness. Training loss alone is never a gate.
|
| 52 |
+
|
| 53 |
+
### Observed-transition gate
|
| 54 |
+
|
| 55 |
+
Use fixed same-replica transitions at exactly 50 frames. For each transition,
|
| 56 |
+
score persistence, the mean error of individual stochastic samples, best of
|
| 57 |
+
K, the ensemble-mean endpoint, displacement-magnitude error, and displacement
|
| 58 |
+
direction cosine after the same C-alpha alignment policy.
|
| 59 |
+
|
| 60 |
+
Before any standard-test access, a candidate must on the validation suite:
|
| 61 |
+
|
| 62 |
+
1. improve ensemble-mean endpoint RMSD over the pinned source MarS-FM model;
|
| 63 |
+
2. beat persistence with a protein-level 95% bootstrap confidence interval
|
| 64 |
+
excluding zero;
|
| 65 |
+
3. improve on a majority of validation proteins, not only pooled transitions;
|
| 66 |
+
4. retain the result for at least three training seeds.
|
| 67 |
+
|
| 68 |
+
Best-of-K is diagnostic only because it uses the unknown future to select a
|
| 69 |
+
sample.
|
| 70 |
+
|
| 71 |
+
### Equilibrium-ensemble retention gate
|
| 72 |
+
|
| 73 |
+
On matched tree samples and MD references, report DCCM error, RMSF error and
|
| 74 |
+
correlation, pairwise-distance Wasserstein distance, reference-PCA covariance
|
| 75 |
+
error/RMSIP, contact-transition Wasserstein distance, radius-of-gyration
|
| 76 |
+
Wasserstein distance, and clash rate. A kinetic gain cannot promote a model
|
| 77 |
+
that materially degrades the source model's equilibrium or structural
|
| 78 |
+
behavior. The one-protein `1e7uA04` comparison is a development pilot only;
|
| 79 |
+
promotion requires a protein-level validation aggregate.
|
| 80 |
+
|
| 81 |
+
## Promotion boundary
|
| 82 |
+
|
| 83 |
+
Passing this protocol only freezes a candidate. The 495-domain standard
|
| 84 |
+
mdCATH test split remains unopened until architecture, checkpoint, sampling
|
| 85 |
+
settings, seeds, metrics, and failure policy are immutable. A field-level
|
| 86 |
+
claim additionally requires matched runnable baselines, protein-level
|
| 87 |
+
uncertainty, replica-noise comparisons, and independent external replication.
|
| 88 |
+
|
receipts/equilibrium-suite-comparison.json
ADDED
|
@@ -0,0 +1,616 @@
|
|
|
|
|
|
|
|
|
|
|
|
|
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receipts/full-transition-comparison.json
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@@ -0,0 +1,284 @@
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| 1 |
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| 2 |
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| 3 |
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| 4 |
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receipts/head-to-head-vs-previous-senba.json
ADDED
|
@@ -0,0 +1,284 @@
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| 1 |
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receipts/replications/seed2/compact-transition-comparison.json
ADDED
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@@ -0,0 +1,104 @@
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|
| 1 |
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| 2 |
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receipts/replications/seed2/interpolation-result.json
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receipts/replications/seed2/parent-result.json
ADDED
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receipts/replications/seed3/compact-transition-comparison.json
ADDED
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20260827
|
| 75 |
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],
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| 76 |
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|
| 77 |
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| 78 |
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| 79 |
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| 80 |
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| 81 |
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|
| 82 |
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"training_elapsed_seconds_mean": 126.070320562,
|
| 83 |
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"compact_panel_proteins_per_seed": 8,
|
| 84 |
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"ensemble_mean_rmsd_improvement_vs_source_angstrom": [
|
| 85 |
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0.030089207430793796,
|
| 86 |
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0.022905611767840894,
|
| 87 |
+
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|
| 88 |
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],
|
| 89 |
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"ensemble_mean_rmsd_improvement_vs_source_angstrom_mean": 0.027335799749363696,
|
| 90 |
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"proteins_better_than_source_per_seed": [
|
| 91 |
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8,
|
| 92 |
+
8,
|
| 93 |
+
8
|
| 94 |
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],
|
| 95 |
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"matched_improvement_vs_previous_senba_angstrom": [
|
| 96 |
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|
| 97 |
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|
| 98 |
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|
| 99 |
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|
| 100 |
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"matched_improvement_vs_previous_senba_angstrom_mean": 0.0025157610124321165
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| 101 |
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},
|
| 102 |
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"campaign_compute": {
|
| 103 |
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"workspace": "daddyjj43",
|
| 104 |
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"billing_date": "2026-08-25",
|
| 105 |
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"observed_modal_cost_usd": 19.451563639999996,
|
| 106 |
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"adaptation_cost_usd": 10.601034570000001,
|
| 107 |
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"validation_cost_usd": 8.85052907,
|
| 108 |
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"note": "This includes the epoch sweep, interrupted and rejected runs, anchor search, equilibrium validation, full-panel validation, and seed replications. It is larger than the cost of the selected training run alone."
|
| 109 |
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},
|
| 110 |
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"artifacts": {
|
| 111 |
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"checkpoint": "frozen-candidate/seed1/mars-fm-e010-a07350-exactlag-128x32-20260825-s1-v1/checkpoints/best.ckpt",
|
| 112 |
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"full_transition_comparison": "full-transition/e010-a07350-comparison.json",
|
| 113 |
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"full_head_to_head_comparison": "head-to-head/e010-vs-old-full.json",
|
| 114 |
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"equilibrium_comparison": "equilibrium-suite/e010-a07350/comparison.json",
|
| 115 |
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"seed_2_replication": "e010-seed-replication/s2/comparison.json",
|
| 116 |
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"seed_3_replication": "e010-seed-replication/s3/comparison.json"
|
| 117 |
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},
|
| 118 |
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"test_records_opened": 0,
|
| 119 |
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"claim_boundary": "validation_only_not_test_or_sota_evidence"
|
| 120 |
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}
|
release-manifest.json
ADDED
|
@@ -0,0 +1,121 @@
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
|
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|
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|
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|
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|
|
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|
|
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|
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|
|
|
|
|
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|
|
|
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|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
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|
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|
|
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|
|
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|
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|
|
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|
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|
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|
|
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|
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|
|
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|
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|
|
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|
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|
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|
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|
|
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|
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|
|
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|
| 1 |
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{
|
| 2 |
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|
| 3 |
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|
| 4 |
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|
| 5 |
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|
| 6 |
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| 7 |
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senba.ckpt
ADDED
|
@@ -0,0 +1,3 @@
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|
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|
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