ArticleJournal of the American Chemical Society2018
Fundamental Insights into Proton-Coupled Electron Transfer in Soybean Lipoxygenase from Quantum Mechanical/Molecular Mechanical Free Energy Simulations.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Donor-Acceptor Separation Augments Temperature Dependence of Kinetic Isotope Effects in NADH Model Hydride Transfer Reactions: Mimicking Enzyme versus Mutant Dynamics.The journal of physical chemistry. B · 2026Article
- Free energy relationship analysis for temperature dependence of hydride kinetic isotope effects of NADH/NADChemical science · 2026Article
- Activation and execution of lipoxygenase catalysis.Redox biochemistry and chemistry · 2026Article
- Computational Method for the Detection of Communication Pathways in Enzymes that Correlate with Experimentally Defined Thermal Activation Networks.The journal of physical chemistry letters · 2026Article
- Mapping Strigolactone Hydrolysis in DWARF14 via QM/MM String Method.bioRxiv : the preprint server for biology · 2026Article
- Quantum medicine: A quantum-mechanical framework for redox biology, disease and precision medicine.Clinical and translational medicine · 2026Review
- Correlated Motion-Based Residue Network Analysis Reveals the Distal Thermal Activation in Soybean Lipoxygenase.bioRxiv : the preprint server for biology · 2025Article
- Tutorial on computing nonadiabatic proton-coupled electron transfer rate constants.The Journal of chemical physics · 2025Article
- A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025Review
- Explaining Kinetic Isotope Effects in Proton-Coupled Electron Transfer Reactions.Accounts of chemical research · 2025Article
- Physics-based modeling in the new era of enzyme engineering.Nature computational science · 2025Review
- Delayed-Onset Muscle Soreness Begins with a Transient Neural Switch.International journal of molecular sciences · 2025Review
- Rigidity Analysis of Hydride Tunneling Ready States from Secondary Kinetic Isotope Effects and Hammett Correlations: Relating to the Temperature Dependence of Kinetic Isotope Effects.Journal of physical organic chemistry · 2025Article
- Structural Effects on the Hydride-Tunneling Kinetic Isotope Effects of NADH/NADThe Journal of organic chemistry · 2025Article
- Hydrogen Tunneling and Conformational Motions in Nonadiabatic Proton-Coupled Electron Transfer between Interfacial Tyrosines in Ribonucleotide Reductase.Journal of the American Chemical Society · 2025Article
- Surface-Accelerated String Method for Locating Minimum Free Energy Paths.Journal of chemical theory and computation · 2024Article
- Probing Nonadiabaticity of Proton-Coupled Electron Transfer in Ribonucleotide Reductase.The journal of physical chemistry letters · 2024Article
- Article
- Exploring Proton-Coupled Electron Transfer at Multiple Scales.Nature computational science · 2023Article
- Temporal and spatial resolution of distal protein motions that activate hydrogen tunneling in soybean lipoxygenase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The proton-coupled electron transfer (PCET) reaction catalyzed by soybean lipoxygenase has served as a prototype for understanding hydrogen tunneling in enzymes. Herein this PCET reaction is studied with mixed quantum mechanical/molecular mechanical (QM/MM) free energy simulations. The free energy surfaces are computed as functions of the proton donor-acceptor (C-O) distance and the proton coordinate, and the potential of mean force is computed as a function of the C-O distance, inherently including anharmonicity. The simulation results are used to calculate the kinetic isotope effects for the wild-type enzyme (WT) and the L546A/L754A double mutant (DM), which have been measured experimentally to be ∼80 and ∼700, respectively. The PCET reaction is found to be exoergic for WT and slightly endoergic for the DM, and the equilibrium C-O distance for the reactant is found to be ∼0.2 Å greater for the DM than for WT. The larger equilibrium distance for the DM, which is due mainly to less optimal substrate binding in the expanded binding cavity, is primarily responsible for its higher kinetic isotope effect. The calculated potentials of mean force are anharmonic and relatively soft at shorter C-O distances, allowing efficient thermal sampling of the shorter distances required for effective hydrogen tunneling. The primarily local electrostatic field at the transferring hydrogen is ∼100 MV/cm in the direction to facilitate proton transfer and increases dramatically as the C-O distance decreases. These simulations suggest that the overall protein environment is important for conformational sampling of active substrate configurations aligned for proton transfer, but the PCET reaction is influenced primarily by local electrostatic effects that facilitate conformational sampling of shorter proton donor-acceptor distances required for effective hydrogen tunneling.
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