Quantum Vibrations in Virus Binding Reveal Faster Electron Transfer Mechanisms

Researchers are increasingly focused on understanding electron transfer dynamics within biological systems, and a new study by Haseeb and Toutounji, both from United Arab Emirates University, delves into the quantum mechanics governing this process in the SARS-CoV-2 Spike protein bound to the human ACE2 receptor. Their work investigates how vibrational interactions between these proteins reshape electron transfer beyond the traditional Condon approximation, utilising a Non-Markovian Stochastic Schrödinger Equation approach.

This research is significant because it demonstrates that nuclear motion can dynamically control electron tunneling, potentially revealing a molecular recognition mechanism where vibrational assistance and coherence play a crucial role in ACE2-Spike binding, and offering new insights into viral interaction processes. The study demonstrates that when environmental dynamics are considered beyond the simplified Markovian limit, population dynamics exhibit non-exponential decay and coherent oscillatory features. These observations indicate a heightened sensitivity to the vibrational frequency of the Spike protein, suggesting a more complex interaction than previously understood. Incorporating off-diagonal system, bath coupling alongside diagonal coupling further elucidates that nuclear motion can dynamically regulate electron tunneling, effectively sharpening the frequency selectivity of the VA-ET mechanism. Furthermore, a structured environmental spectral density, characterised by long-lived correlations, preserves electronic, vibrational coherence for extended periods, amplifying the vibrational selectivity of this molecular switch. These findings support the hypothesis that the ACE2, Spike interaction may leverage vibrational assistance and quantum coherence as a molecular recognition mechanism, potentially offering new insights into the initial stages of viral infection. The research suggests that specific vibrational modes within the Spike protein could act as a “switch”, modulating electron transfer in the ACE2 receptor and influencing the binding process. This detailed analysis, focusing on the quantum dynamics of ligand, receptor electron transfer, reveals that the biological environment surrounding ACE2 and Spike exhibits non-Markovian dynamics, meaning the system’s past influences its present state. Traditional Markovian models, which assume rapid environmental relaxation, fail to capture these crucial memory effects. The inclusion of non-Condon effects, where nuclear motions modulate electronic coupling, further refines the understanding of VA-ET, demonstrating that nuclear motion can dynamically gate electron tunneling. These discoveries have broader implications for understanding biological electron transfer in complex environments and may pave the way for novel antiviral strategies targeting the ACE2, Spike interaction. Modelling the ACE2 receptor-Spike protein interaction using non-Markovian quantum dynamics A Non-Markovian Quantum State Diffusion (NMQSD) formalism underpins the work, allowing simulation of the reduced quantum state of the ACE2 receptor and a relevant Spike protein mode under a realistic environmental influence without perturbative expansions. The study models the ACE2 receptor’s redox-active site as a two-level system with a donor state |D⟩ and an acceptor state |A⟩, described by a Hamiltonian HTLS = ε/2 σz + ∆/2 σx, where σz and σx are Pauli matrices and ε represents the energy bias between states. The Spike protein is represented by a single vibrational degree of freedom, a harmonic oscillator with Hamiltonian Hvib = ħωv b†b, where ωv is the angular frequency of the mode and b†/b are creation/annihilation operators. Coupling between the ACE2 electronic states and the Spike vibrational mode is established via an interaction term HDA-vib = γ σz (b + b†), representing that the occupancy of donor versus acceptor states is coupled to the vibrational mode’s displacement. Simulations employ many stochastic quantum trajectories, each representing a possible realization of environmental noise, to obtain ensemble dynamics equivalent to solving a non-Markovian master equation. Verification of the approach involved demonstrating reproduction of classical Marcus, Jortner kinetics under high-temperature, fast-relaxing bath, and weak off-diagonal coupling conditions, providing a consistency check. Beyond these limits, the research explores strong coupling, mid-frequency vibrational assistance, and structured environmental noise to uncover factors affecting the efficiency and specificity of vibrationally assisted electron transfer. The system-bath coupling incorporates both diagonal and off-diagonal terms, enabling investigation of how nuclear motion dynamically gates electron tunneling and sharpens the frequency selectivity of the VA-ET mechanism. The research details electron transfer between donor and acceptor states within the human ACE2 receptor, modulated by a specific vibrational mode of the SARS-CoV-2 Spike protein. Analysis of environmental (non-Markovian dynamics) and non-Condon effects (vibrational modulation of electronic coupling) demonstrates the complex interplay governing this process. In the Markovian limit, with an Ohmic bath, extracted transfer rates align with semiclassical Marcus, Jortner predictions within the appropriate energy regime. However, incorporating off-diagonal system, bath coupling alongside diagonal coupling shows that nuclear motion can dynamically gate electron tunneling, sharpening the frequency selectivity of the vibrationally-assisted electron transfer (VA-ET) mechanism. This dynamic gating significantly influences the pathway of electron transfer, enhancing its precision. Furthermore, a structured (sub-Ohmic) environmental spectral density, characterised by long-lived correlations, preserves electronic, vibrational coherence over extended timescales. This preservation amplifies vibrational selectivity under non-Condon coupling, suggesting a heightened responsiveness to specific vibrational frequencies. The study establishes that these long-lived correlations, indicative of “memory” within the system, are crucial for maintaining coherence and enhancing selectivity. These results support the proposition that the ACE2, Spike interaction may exploit vibrational assistance and quantum coherence as a molecular recognition mechanism. The work investigates the dynamics of ligand, receptor electron transfer and conformational response, treating the ACE2, Spike interface as an open system embedded within a biological environment. Computational modelling focused on vibrational modes within the range of 800cm−1 to 1600cm−1, frequencies relevant to key chemical bond motions potentially assisting electron tunneling. Non-Markovian dynamics govern electron transfer at the SARS-CoV-2 spike-ACE2 interface Researchers investigated electron transfer and conformational changes within the SARS-CoV-2 Spike protein bound to the human ACE2 receptor, modelling the interaction as an open quantum system within a biological environment. The study demonstrated that, under conditions resembling a fast-relaxing environment and high temperature, the model aligned with established Marcus, Jortner theory of electron transfer. However, deviations from these conditions resulted in non-exponential decay, coherent oscillations, and increased sensitivity to vibrational frequency, highlighting the necessity of a quantum mechanical approach for accurate modelling. A structured environment, typical of proteins within cell membranes, preserved quantum coherence and amplified vibrational selectivity, while incorporating off-diagonal coupling showed that nuclear motion can dynamically control electron tunneling, enhancing the frequency selectivity of vibrationally assisted electron transfer. These findings support the hypothesis that ACE2-Spike binding may utilise vibrational assistance and coherence as a molecular recognition mechanism, potentially influencing infectivity. The authors acknowledge that the proposition of electron transfer triggering ACE2 conformational change remains speculative, though their quantitative model provides a framework for testing such hypotheses. Limitations include the reliance on a specific vibrational mode of the Spike protein and the simplified representation of the biological environment. Future research could explore the impact of mutations in the Spike protein on vibrational dynamics and electron transfer rates, and investigate whether electron transfer genuinely occurs upon ACE2 binding and contributes to cell entry. These investigations may reveal whether the Spike protein’s vibrational characteristics have been evolutionarily optimised to facilitate infection. 👉 More information 🗞 Quantum Dynamics of Vibrationally-Assisted Electron Transfer beyond Condon approximation in the Ligand-Receptor Complex 🧠 ArXiv: https://arxiv.org/abs/2602.06469 Tags: