Udoisoh Moses G, Adegoke Olusola Olaitan, James Amy Lebua
Photonics and Theoretical Solid State Physics Unit, Department of Physics, Ignatius Ajuru University of Education, Rumuolumeni, Rivers State, Nigeria.
Department of Biochemistry, Joseph Ayo Babalola University, Ikeji, Osun State, Nigeria.
J Mol Model. 2025 Jul 29;31(8):221. doi: 10.1007/s00894-025-06447-z.
This study establishes a quantum-biophysical framework for non-invasive opioid overdose reversal by demonstrating ultrafast terahertz (THz) torque-mediated disruption of fentanyl-μ-opioid receptor (μOR) binding. By targeting the vibrational modes of the fentanyl-μOR complex with resonant THz pulses (1-1.5 THz, ≥ 100 kV/cm), the study examines two key binding configurations: the Asp147 salt bridge (D147) and His297 hydrogen bond (H297). The model reveals that THz-induced torque reduces the dissociation barrier by 3.2-3.8 kcal/mol through mechanical disruption of the N-H⁺···O⁻ interaction, achieving 50% unbinding within 1.2 ps at optimal frequencies. The H297 configuration dissociates 40% faster than D147, indicating a pharmacologically preferable site for intervention. A sigmoidal dose-response is observed in the 100-150 kV/cm range, enabling > 90% dissociation efficacy under non-thermal conditions. These findings offer a novel electromagnetic approach for modulating opioid pharmacodynamics and inform the development of receptor-targeted antidotes via precision bioelectromagnetic strategies. While this study demonstrates the theoretical feasibility of THz-induced dissociation, future experimental work is needed to address translational challenges such as tissue penetration and biological specificity.
The study employs a quantum-classical hybrid framework combining time-dependent Schrödinger equation simulations with classical electrodynamics. Fentanyl is modeled as a confined asymmetric rotor interacting with a µOR-like potential landscape under circularly polarized THz radiation. Quantum torque is derived from angular momentum operators coupled to the electric field vector. Site-specific binding configurations (D147 and H297) are simulated with field-driven vibrational excitation and potential energy surface deformation. Dissociation dynamics and barrier modulation are quantified using Fermi's Golden Rule and time-evolved wavepacket propagation. Numerical computations were performed in Wolfram Mathematica 13.1, with molecular input parameters validated against DFT-based dipole moments, mass tensors, and force-field data extracted from experimental literature.
本研究通过展示超快太赫兹（THz）扭矩介导的芬太尼 - μ阿片受体（μOR）结合的破坏，建立了一种用于无创阿片类药物过量逆转的量子生物物理框架。通过用共振太赫兹脉冲（1 - 1.5 THz，≥100 kV/cm）靶向芬太尼 - μOR复合物的振动模式，该研究考察了两种关键的结合构型：天冬氨酸147盐桥（D147）和组氨酸297氢键（H297）。该模型表明，太赫兹诱导的扭矩通过对N - H⁺···O⁻相互作用的机械破坏使解离势垒降低3.2 - 3.8 kcal/mol，在最佳频率下1.2 ps内实现50%的解离。H297构型的解离速度比D147快40%，表明这是一个药理学上更适合干预的位点。在100 - 150 kV/cm范围内观察到S形剂量反应，在非热条件下可实现>90%的解离效率。这些发现为调节阿片类药物的药效学提供了一种新的电磁方法，并通过精确的生物电磁策略为受体靶向解毒剂的开发提供了信息。虽然本研究证明了太赫兹诱导解离的理论可行性，但未来还需要进行实验工作来解决诸如组织穿透和生物特异性等转化挑战。
该研究采用了一种量子 - 经典混合框架，将含时薛定谔方程模拟与经典电动力学相结合。芬太尼被建模为一个受限的不对称转子，在圆偏振太赫兹辐射下与类似μOR的势能面相互作用。量子扭矩由与电场矢量耦合的角动量算符导出。通过场驱动的振动激发和势能面变形来模拟位点特异性结合构型（D147和H297）。使用费米黄金规则和时间演化波包传播来量化解离动力学和势垒调制。数值计算在Wolfram Mathematica 13.1中进行，分子输入参数根据基于密度泛函理论的偶极矩、质量张量以及从实验文献中提取的力场数据进行了验证。
