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SMA Research Platform

Evidence graph for Spinal Muscular Atrophy

Biology-first target discovery
Christian Fischer / Bryzant Labs
—Targets
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Compound Pipeline

Compounds ranked by multi-fidelity Bayesian scoring across 4 layers: Docking (w=0.15), ADMET (w=0.25), MD Stability (w=0.35), Binding (w=0.25). Safety badges from ADMET-AI GNN predictions.

v2.1 Evidence-First Pipeline — 11 Stages
0
GenMol
›
1
ADMET
›
1.5
Retro
›
2
Safety
›
3a
Dock
›
3b
InducedFit
›
4
Select
›
5
MD
›
6
FreeE
›
7
Ortho
›
8
Lab
completed
in progress
failed
pending

Stage 0: Generative design (GenMol NIM) · Stage 1: ADMET-AI GNN 27 endpoints · Stage 1.5: Retrosynthesis (AiZynthFinder) · Stage 2: Safety gate · Stage 3a: Rigid docking (FlowDock) · Stage 3b: Induced-fit (NeuralPLexer3) · Stage 4: Selectivity filter · Stage 5: MD simulation (OpenMM) · Stage 6: Free energy (BindFlow FEP) · Stage 7: Orthogonal assay · Stage 8: Lab validation

▶How does Compound Scoring work?

Compounds are ranked by a multi-fidelity Bayesian score combining four computational evidence layers. Missing layers widen the confidence interval rather than penalizing the score.

  • Docking (w=0.15) — FlowDock pose confidence + Vina binding energy. Low weight: fast but coarse. Min 5 poses per compound.
  • ADMET (w=0.25) — ADMET-AI GNN: BBB penetration, hepatotoxicity, hERG liability, solubility, CYP inhibition. Score = fraction of safety-passed endpoints.
  • MD Stability (w=0.35)— 100ns OpenMM simulation. RMSD <3A and stable pose over final 20ns required. Highest weight: measures residence time directly.
  • Binding Free Energy (w=0.25) — MMPBSA/BindFlow FEP from MD trajectory. Units: kcal/mol. More negative = stronger binding.

score = sum(layer * weight) / sum(weights_present). Status: early = docking only, promising = ADMET + MD, ready = all 4 layers.

Data source:sma-research/campaigns/— per-target campaign folders with full ADMET / docking / MD / scoring data
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