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Senba release: mars-fm-e010-a07350-exactlag-128x32-20260825-s1-v1 (validation-only)

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LICENSE ADDED
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+ MIT License
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+
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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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+
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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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+
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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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+
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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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+
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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.
README.md ADDED
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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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+
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+ # Senba
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+
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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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+
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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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+
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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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+
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+ Release page: <https://senba.papercrane.bio/>
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+
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+ ## Identity
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+
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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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+
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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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+
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+ ## How it was made
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+
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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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+
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+ ## Evidence
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+
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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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+
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+ ### Full eligible validation panel (28 domains, ≤256 residues)
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+
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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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+
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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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+
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+ ### Equilibrium retention (8 domains, official tree sampling, 500 samples)
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+
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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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+
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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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+
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+ ### Replication (three independently trained parents, 8-domain compact panel)
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+
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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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+
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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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+
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+ ### Negative results that remain part of the evidence
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+
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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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+
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+ ## Intended use
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+
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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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+
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+ ## How to run
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+
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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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+
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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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+
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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.
154
+ A GPU is recommended; CPU works but is slow.
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+
156
+ To load the checkpoint yourself, follow `inference_example.py`: build the same batch layout as
157
+ MarS-FM (`torsions`, `torsion_mask`, `trans`, `rots`, `seqres`, `mask`), then call
158
+ `MarSModule.inference(batch, num_steps=10)`.
159
+
160
+ ## Files
161
+
162
+ | Path | Contents |
163
+ | --- | --- |
164
+ | `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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+ | `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 |
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+ | `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
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+ #!/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 @@
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
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