Nucleated Self-Excitation: Conformational Propagation and Self-Sustained Excitation in Proteins, and a Universal Mechanism

Two established phenomena of protein science—nucleation-dependent polymerization and prion-type conformational propagation—share a mechanistic core that lacks an operational criterion: what makes a conformational excitation self-sustaining. This paper derives a complete reasoning chain from the atomic level: conformational states as multiple minima on the energy landscape; the duality of the excited state (a misfolded molecule is simultaneously an attenuator and an exciter); competition of two rates (excitation transfer beta vs spontaneous decay gamma); crossing one (self-sustained propagation, a gain chain); population coherence; macroscopic nucleation. Operational definitions and a three-layer criterion: mechanism (rate ratio crossing one), morphology (residence-time ratio), maintenance (dual survival conditions). Quantitative evidence: lag phase and seeding reinterpreted; ice as a physical fuse (four experimental strands); carbon-protein two-stage fuse; contrast with autocatalytic-set theory (connected-but-not-sustaining operational distinction). The same criterion holds across chemical replication, ecological colonization and epidemic spread (R0=beta/gamma). Physical waves are treated in the companion paper. [v1.2: first-round data test added (Section 4.1b)—log-linearity of lag vs ln(seed) across four systems (prion RT-QuIC, IAPP x2, tau; 3/4 AIC-strong), slope-inverted beta-gamma positive throughout, independent cross-validation ratio 1.23 vs literature globally-fitted rates.]