Hydration–Geometry Transduction: A Falsifiable Mechanistic Framework for Receptor-State Transduction

Hydration–Geometry Transduction (HGT) is proposed as a falsifiable mechanistic framework for receptor-state transduction. The central hypothesis is that stimulus-driven molecular events shift a coupled protein–hydration free-energy landscape and that predeclared hydration-state variables can, in selected receptor systems, add reproducible out-of-sample predictive value beyond direct chemistry, protein geometry, and conventional bulk-solvent descriptors. The present version formalizes a nested test architecture: Model C (conventional), Model H = C + hydration-state vector H(t), and Model M = H + predeclared microtubule-associated variables. Rhodopsin remains a particularly clean discriminator because the initiating photon carries no external hydration shell; osmotic/thermodynamic experiments infer an activation-associated hydration increase equivalent to approximately 80–100 water molecules. Our RHO-S0.1 static structural robustness extension evaluates compatible Dark (1U19, 3C9L) and Meta-II (3PXO, 3PQR) models against same-state/modeling controls. Across all nine frozen probe×mask conditions, the weakest Dark↔Meta-II Q_reconfig exceeds the strongest included same-state/modeling control, with Jaccard separation in the same direction; the public archive reproduces with 28/28 automated checks passing. RHO-S0.1 quantifies water-size-compatible static geometric accessibility. MT-associated state is a separate second-stage test after the receptor-level HGT gate.