Mechanism of quantum-entanglement–enhanced pH ultra-sensitivity in SITE-pHorin

Determine the detailed quantum-chemical mechanism by which quantum entanglement between residue Y182 and the chromophore in the fluorescent protein SITE-pHorin generates pH ultra-sensitivity across physiological pH, clarifying how Y182 deprotonation and the chromophore’s benzene-ring curvature contribute to the effect.

Background

SITE-pHorin is a genetically encoded, ratiometric pH sensor engineered from mTurquoise2 that exhibits single-excitation dual-emission behavior and unusually high pH sensitivity across pH 3.5–9.0. Structural analyses showed opposite protonation states between the phenolic hydroxyl of residue Y182 (outside the β-barrel) and the chromophore under different pH conditions, a phenomenon the authors interpret as evidence of quantum entanglement mediating pH sensing.

Computational modeling (DFT) and a perturbation mutant (C203E) suggest that Y182 deprotonation alone is insufficient to explain the observed coupling and that a discrete curvature of the chromophore’s benzene ring may also be necessary. Despite these insights, the precise mechanism by which quantum entanglement produces the observed pH ultra-sensitivity in SITE-pHorin remains to be established.