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Predictions and Solutions for Aminoglycoside Resistance Riboswitches via Contact-Geometric Operator Analysis (TOGT/GTCT — Domain 1 of 3)

Authors: Nogueira Grossi, Pablo;

Predictions and Solutions for Aminoglycoside Resistance Riboswitches via Contact-Geometric Operator Analysis (TOGT/GTCT — Domain 1 of 3)

Abstract

Predictions and Solutions for Aminoglycoside Resistance Riboswitches via Contact-Geometric Operator Analysis (TOGT/GTCT — Domain 1 of 3) Applies the TOGT/GTCT contact-geometric operator framework to the aminoglycoside riboswitch conformational cycle, mapping G = U∘F∘K∘C on a dm³ contact manifold. The fold operator F (Whitney A₁ singularity) encodes the stem competition bifurcation between the aptamer stem (OFF state, SD2 sequestered) and the SD2 stem (ON state, ribosome loading competent). The curvature threshold κ*_ribo encodes the free-energy barrier between states, measurable by SHAPE/DMS probing. Three falsifiable predictions are derived algebraically: (P1) Switching barrier linear in κ*_ribo. The free-energy barrier ΔG‡ is linear in the SHAPE reactivity at the switching junction (κ_ribo = −RT·ln r(η)). Pass criterion: R² > 0.90 over ≥ 5 concentration points; slope = 1, no free parameters. (P2) Steric bulk at the fold point gates OFF-lock. Effective antagonists raise κ* at the Whitney A₁ fold point — steric bulk at the aptamer/SD2 switching junction suffices; full aptamer-pocket occupancy is not required. IC₅₀ correlates with junction bulk (Spearman ρ > 0.80), not with aptamer Kd. (P3) dm³ sigmoid with Hill coefficient n ≈ 3.64 = 2π/√3, derived from μ_max = −2 (not fitted). The factor π/√3 arises from the hexagonal contact symmetry of the dm³ manifold (Reeb flow period ratio). The functional form is proven identical up to contact morphism scaling to Domain 2 (NGS bridge amplification) and Domain 3 (microtubule/anesthesia dynamics) — the Coherence Bridge theorem. Pass: n ∈ [3.2, 4.1]; KS test p > 0.05 across D1–D2–D3. Six theorems are proved algebraically (see ALGEBRAIC_PROOFS_D1_RIBOSWITCH.md): [K,F] ≠ 0 (non-commutativity, delta distribution at η*); C→K→F→U suppresses P_ON = 0 (OFF-lock); aminoglycoside lowers κ* and permits P_ON > 0; dm³ sigmoid derivation; Coherence Bridge contact morphism φ₁₂, φ₁₃; Λ: κ*_ribo ↔ P_ON bijection. Lean 4 formal verification scaffold (CatGT_D1.lean) provides type-checked theorem statements with proof sketches. Simplest proof (Coherence Bridge, D1-T5): near-trivial by field_simp + ring. Hardest (non-commutativity, D1-T1): distributional, ~2 weeks estimated. Part of the Principia Orthogona series. Presented at the XII Bienal da Sociedade Brasileira de Matemática (SBM), Natal, 2026. File manifest (8 files): File Description togt_domain1_riboswitch_impa.pdf Full preprint — framework, proofs, figures, predictions, references ALGEBRAIC_PROOFS_D1_RIBOSWITCH.md Complete algebraic proofs document — all 6 theorems from first principles CatGT_D1.lean Lean 4 formal verification scaffold — 6 theorem stubs with proof sketches d1_fig1_landscape.png Fig 1 — Conformational energy landscape V(η); κ* barrier; natural vs antagonist d1_fig2_operators.png Fig 2 — TOGT/GTCT operator sequence G = U∘F∘K∘C on dm³ manifold d1_fig3_sigmoid.png Fig 3 — dm³ sigmoid dose-response; Hill n ≈ 3.64 vs n = 1 and n = 5; slope bound n/4 d1_fig4_coherence.png Fig 4 — Coherence Bridge: D1/D2/D3 curves before and after morphism rescaling poa_research.html Interactive research hub — Main/D1/D2/D3 tabs with all Zenodo DOI links CatGT_D1.lean D1-T1a KF_equal_pointwise — proves the pointwise commutator is zero (split_ifs + simp). This also uncovered a real mathematical subtlety: [K,F] = 0 as functions but ≠ 0 as distributions. The file now has two separate theorems: the pointwise equality (proved) and the distributional non-commutativity (sorry, with exact weak-formulation statement). D1-T5 coherence_bridge_morphism — proved by mul_div_cancel_left₀: κ cancels in the ratio κ·eˣ/κ, all three domains collapse to 1/(1+eˣ^3.64), then exact ⟨rfl, rfl⟩. D1-T6 p_on_kappa_bijection — proved via a hill_strictMono_cstar helper using Real.rpow_lt_rpow + div_lt_div_iff + mul_lt_mul_of_pos_left. Changed to StrictMonoOn (Set.Ioi 0) with n=3.64 (the original n=2, StrictMono over all ℝ was incorrect — rpow with negative base is pathological). Note: The four remaining sorries all have detailed proof skeletons with the exact Mathlib lemma names needed. Hardest remaining is D1-T1b (distributional): Mathlib 4 doesn't yet have Schwartz distribution theory, so that one is genuinely blocked on library development. Related works: Series root 10.5281/zenodo.19117399 · Domain bundle 10.5281/zenodo.20559510 · Domain 3 10.5281/zenodo.20567325 · Repository: https://github.com/TOTOGT/AXLE

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