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

Quantum-Topological Simulation of Berry Phase-Induced Fentanyl-μ-Opioid Receptor Dissociation via Terahertz Vortex Fields | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Quantum-Topological Simulation of Berry Phase-Induced Fentanyl-μ-Opioid Receptor Dissociation via Terahertz Vortex Fields Moses G. Udoisoh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7375252/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Journal of Molecular Modeling → Version 1 posted 7 You are reading this latest preprint version Abstract 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. Geometric phase Terahertz vortex fentanyl opioid receptor quantum control topological chemistry Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 20 Nov, 2025 Read the published version in Journal of Molecular Modeling → Version 1 posted Editorial decision: Revision requested 09 Sep, 2025 Reviews received at journal 04 Sep, 2025 Reviewers agreed at journal 21 Aug, 2025 Reviewers invited by journal 21 Aug, 2025 Editor assigned by journal 18 Aug, 2025 Submission checks completed at journal 18 Aug, 2025 First submitted to journal 14 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7375252","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508098929,"identity":"f45fcce6-ea2c-4bf4-9209-a930c75147ec","order_by":0,"name":"Moses G. 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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.\u003c/p\u003e\n\u003cp\u003eMethod\u003c/p\u003e\n\u003cp\u003eWe 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\u003csub\u003eB\u003c/sub\u003e 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. 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