ArticleThe journal of physical chemistry. B2016
How Large Should the QM Region Be in QM/MM Calculations? The Case of Catechol O-Methyltransferase.
Article in The journal of physical chemistry. B, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- Are QM/MM models systematically improvable? A case study on carbonic anhydrase binding affinities.Journal of computer-aided molecular design · 2026Article
- Bridging the accuracy-speed divide in reactive molecular dynamics with QuantaMind MD.Science advances · 2026Article
- QM/MM Reveals Coordination Shift behind Early Lanthanide Preference in Methanol Dehydrogenase XoxF.The journal of physical chemistry. B · 2026Article
- Enabling Biomolecular Simulations with Neural Network Potentials in GROMACS.Journal of chemical theory and computation · 2026Article
- Methods for the establishment of enzymatic mechanisms - from QM to ML.Chemical science · 2026Review
- Article
- Computational Investigation of GNMT-Catalyzed Methyl Transfer Reaction: Integrating MD, QM, and ML Approaches.Journal of computational chemistry · 2026Article
- pyEF: A Python Framework for QM and QM/MM Atom-Wise Electric Field Analysis.Journal of chemical theory and computation · 2026Article
- QuantumPDB: A Workflow for High-Throughput Quantum Cluster Model Generation from Protein Structures.Journal of chemical information and modeling · 2026Article
- Systematically Improvable and Locality Accelerated Enzymatic Reactivity Modeling: Toward Chemical Accuracy at Affordable Cost.Journal of chemical theory and computation · 2026Article
- Energy-Screened Many-Body Expansion for Protein-Ligand Interactions: Examining Convergence for Metalloenzymes Through Seven-Body Interactions.Journal of chemical theory and computation · 2026Article
- Uncertainty Quantification forChemical reviews · 2026Review
- Article
- Ligand-Induced Electronic Response Enables Predictive QM/MM Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Density-Functionalized QM/MM Delivers Chemical Accuracy For Solvated Systems.Journal of chemical theory and computation · 2025Article
- Mechanistic Insights into SAM-Dependent Methyltransferases: A Review of Computational Approaches.International journal of molecular sciences · 2025Review
- Hierarchical Quantum Embedding by Machine Learning for Large Molecular Assemblies.Journal of chemical theory and computation · 2025Article
- The Role of the Unusual 2-Tyr-1-carboxylate Non-heme Iron Motif in the Mechanism of N,N-Dimethylformamidase.ACS catalysis · 2025Article
- Computational Studies of Enzymes for C-F Bond Degradation and Functionalization.Chemphyschem : a European journal of chemical physics and physical chemistry · 2025Review
- The Effects of Conformational Sampling and QM Region Size in QM/MM Simulations: An Adaptive QM/MM Study With Model Systems.Journal of computational chemistry · 2025Article
23 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely used in studies of enzymatic catalysis. Until recently, it has been cost prohibitive to determine the asymptotic limit of key energetic and structural properties with respect to increasingly large QM regions. Leveraging recent advances in electronic structure efficiency and accuracy, we investigate catalytic properties in catechol O-methyltransferase, a prototypical methyltransferase critical to human health. Using QM regions ranging in size from reactants-only (64 atoms) to nearly one-third of the entire protein (940 atoms), we show that properties such as the activation energy approach within chemical accuracy of the large-QM asymptotic limits rather slowly, requiring approximately 500-600 atoms if the QM residues are chosen simply by distance from the substrate. This slow approach to asymptotic limit is due to charge transfer from protein residues to the reacting substrates. Our large QM/MM calculations enable identification of charge separation for fragments in the transition state as a key component of enzymatic methyl transfer rate enhancement. We introduce charge shift analysis that reveals the minimum number of protein residues (approximately 11-16 residues or 200-300 atoms for COMT) needed for quantitative agreement with large-QM simulations. The identified residues are not those that would be typically selected using criteria such as chemical intuition or proximity. These results provide a recipe for a more careful determination of QM region sizes in future QM/MM studies of enzymes.
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