:PROPERTIES:
:CREATED:  [2026-05-24 Sun]
:ID:       9c0d1e2f-3a4b-5c6d-7e8f-9a0b1c2d3e4f
:END:
#+title: The Middle of the Knowledge Tree — From Logic to Nanotechnology
#+filetags: :ideas:knowledge:passepartout:

In the tree of knowledge model, mathematical foundations and formal logic sit at the root. Schafmeister's molecular nanotechnology sits at a high branch — programmable molecules that bind proteins and catalyze reactions. The distance between them is bridged by a chain of formal and empirical domains. This note maps that chain.

**The full stack, root to branch.**

| Layer | What it formalizes | Formal status | Verification model |
|---|---|---|---|
| 0. Logic / Foundations | Proof theory, set theory, type theory, ACL2 axioms | Deductive | Complete — provable from axioms |
| 1. Algebra | Groups, rings, fields, vector spaces, modules | Deductive | Complete |
| 2. Analysis | Real numbers, limits, continuity, calculus, measure theory | Deductive | Complete (in principle; deep results are hard) |
| 3. Geometry / Topology | Manifolds, differential forms, curvature, homotopy | Deductive | Complete |
| 4. Classical Mechanics | Lagrangian/Hamiltonian mechanics, Newtonian dynamics | Deductive | Complete — follows from variational principles |
| 5. Quantum Mechanics | Hilbert spaces, operators, Schrödinger equation, symmetries | Deductive | Complete (the theory is fully formalizable) |
| 6. Statistical Mechanics | Ensembles, partition functions, Boltzmann distribution, entropy | Deductive | Complete (follows from QM + probability) |
| 7. Electrodynamics | Maxwell's equations, potentials, radiation | Deductive | Complete |
| 8. Quantum Chemistry | Born-Oppenheimer, Hartree-Fock, DFT, coupled cluster | Partially deductive | The equations are formal. The necessary approximations (Börn-Oppenheimer, exchange-correlation functional) are not. |
| 9. Molecular Mechanics | Force fields (AMBER, CHARMM, OPLS), potential functions, non-bonded interactions | Empirical parameterization | The simulation is deterministic. The parameters are fitted to experiment. |
| 10. Molecular Dynamics | Integration schemes, thermostats, barostats, periodic boundaries | Deductive mechanics + empirical inputs | The integrator is provable. The force field parameters are not. |
| 11. Chemical Thermodynamics | Binding constants, free energy surfaces, reaction equilibria, solvation | Mixed deductive/empirical | Statistical mechanics is deductive. Solvation models are not. |
| 12. Structural Biochemistry | Protein folding, protein-ligand binding, docking, enzyme kinetics | Largely empirical | Binding affinity prediction is not deductively solvable from first principles. |
| 13. Organic Chemistry | Reaction mechanisms, stereochemistry, functional group transformations | Empirical with formal structure | Reaction mechanisms are modeled, not derived. They are falsifiable hypotheses, not theorems. |
| 14. Molecular Design | Spiroligomer design, shape-programmable molecules, therapeutic targeting | Empirical design space | Design rules are heuristics validated by experiment, not derived from QM. |

**What changes at layer 8.**

The important transition happens between layers 7 and 8. Everything from logic through quantum mechanics and statistical mechanics is fully formalizable — you can write down the equations, derive the consequences, and verify the derivations. This is the domain where ACL2 can prove correctness against first principles.

Layer 8 (quantum chemistry) is where the first irreducible approximation appears. The Born-Oppenheimer approximation is not a theorem — it is an assumption that nuclei and electrons can be treated separately because nuclei are much heavier. This assumption is empirically excellent but not deductively guaranteed. The exchange-correlation functional in DFT is not derivable — it is a functional whose exact form is unknown and must be approximated.

From layer 9 onward, the models are empirical through and through. Force field parameters are fitted to experimental data. Solvation models are calibrated against known solubilities. Binding affinity predictions are validated by binding assays, not derived from Schrödinger's equation. The models are mathematically rigorous (the simulation correctly integrates Newton's equations), but the inputs to those models are not.

**What this means for Passepartout.**

Passepartout can verify the *computation* at every layer. It can prove that:

- The Schrödinger equation is correctly solved for a given Hamiltonian (layer 5/8).
- The molecular dynamics integrator preserves phase space volume (layer 10).
- The docking algorithm correctly explores the defined conformational space (layer 12).

But it cannot verify that the *model* matches reality. The Born-Oppenheimer approximation, the DFT functional, the force field parameters, the solvation model, the scoring function — these are commitments to empirical reality that no verification system can discharge. They are validated by experiment, not by proof.

This is the same structure as Stage 7 in Passepartout's own roadmap: after all computational threats are eliminated, oracular limits and physical reality remain. The verification subsystem can certify that a simulation is internally consistent. It cannot certify that the simulation's assumptions hold in the real world.

**What Passepartout would need in the middle.**

For each layer 1-7 (deductive), Passepartout already has or can generate the formal mathematics. These are theorems and algorithms that ACL2 can verify against axioms.

For each layer 8-14 (empirically parameterized), Passepartout needs:

1. **A formal model** of the equations (the DFT equations, the force field functional form, the MD integrator) — verified against the mathematical theory.
2. **A parameter database** with provenance (force field parameters, basis sets, solvation parameters, scoring function weights) — not proven but curated, versioned, and traceable to experimental sources.
3. **An empirical validation pipeline** that compares computed predictions against experimental measurements and updates the parameter confidence.

The parameter database with provenance is the crucial addition. For Schafmeister's work, this means:

| Empirical parameter set | Source | Passepartout role |
|---|---|---|
| DFT functional parameters | Fitted to known systems | Trace which functional was used for each calculation |
| Force field parameters (AMBER, CHARMM) | Fitted to QM + experiment | Trace parameter provenance; flag known failure regimes |
| Solvation free energies | Calibrated to measured solubilities | Track calibration data and confidence intervals |
| Binding affinity benchmarks | PDBbind, DUD-E, experimental IC50 | Track benchmark provenance; report uncertainty |
| Spiroligomer design rules | Schafmeister's own experimental data | Formalize as knowledge graph with experimental backing |

**The nature of the bridge.**

The middle of the knowledge tree is not a chain of theorems. It is a lattice of formal models scaffolded by empirical commitments. Each layer relies on the formal correctness of the layer below (the QM solver is correct), but also on approximations and parameters that are not deductively justified.

This is not a weakness of the architecture. It is a correct description of the relationship between mathematics and experiment. The bridge from logic to nanotechnology is built from:

- **Formal mathematics** for what can be proven (the core theories, the algorithms, the simulation correctness)
- **Models with provenance** for what cannot be proven but works (the approximations, the force fields, the scoring functions)
- **Empirical validation** for the claim that the models match reality (experimental data, benchmarks, error bars)

Passepartout's contribution is not to eliminate the empirical layers — that is impossible. Its contribution is to make explicit which parts are deductively verified, which are empirically fitted, and what the provenance trail is for every numerical value that enters a computation. The system cannot make chemistry deductive. It can make every computational output traceable to its assumptions.

---

- [[id:f4e5d6c7-b8a9-0c1d-2e3f-4a5b6c7d8e9f][Schafmeister and Clasp]] — the nanotechnology branch
- [[id:1c3ec48b-446c-50d2-b53e-126a81f5143f][Passepartout Architecture]] — where verification lives
- [[id:9c0d1e2f-3a4b-5c6d-7e8f-9a0b1c2d3e4f][Stage 7 — What Remains]] — oracular, physical, and empirical limits
