Quantum-Topological Simulation of Berry Phase-Induced Fentanyl-μ-Opioid Receptor Dissociation via Terahertz Vortex Fields

Context Fentanyl binds the μ-opioid receptor (μOR) with sub-nanomolar affinity and ultra-slow dissociation, limiting the effectiveness of pharmacological antagonists in acute overdose. We propose a non-pharmacological control mechanism in which structured terahertz (THz) fields imprint a geometric (Berry) phase on ligand–receptor coordinates to bias unbinding without bulk heating. Specifically, a near-field THz vortex with orbital angular momentum (ℓ≠0) provides a polarization/phase texture and weak sub-wavelength gradients at the pocket scale, enabling selective actuation of a torsional–proton transfer coordinate relevant to fentanyl–μOR binding. Method We formulate the quantum dynamics on a curved 2D configuration space (r,θ) that encodes steric hindrance and hydrogen-bond deformation, and solve the covariant time-dependent Schrödinger equation using Crank–Nicolson propagation with absorbing boundaries. The driving field is modeled as near-field terahertz vortex (topological charge ℓ≠0) that allows topological charge to enter through the field’s polarization/phase texture after rotation to body-fixed axes. Berry phases were computed on closed (θ,Φ) cycles under an explicit adiabaticity/gap criterion, while Kramers-type rebinding are applied to measure rate enhancement rather than deterministic yields. Simulations indicate an effective torsional barrier reduction of 0.06 eV (≈2.3 k _B T at 300 K) within the 1–1.5 THz band, sufficient to accelerate μOR–fentanyl escape by ~10× at fixed temperature. A value consistent with non-thermal, frequency-addressable biasing of dissociation pathways. These findings establish a quantum-coherent, non-pharmacological strategy for disengaging potent opioid ligands, offering a new pathway for photonic control of Biochemical interactions with sub-molecular precision.