ArticlePhysical chemistry chemical physics : PCCP2018
Large-scale QM/MM free energy simulations of enzyme catalysis reveal the influence of charge transfer.
Article in Physical chemistry chemical physics : PCCP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Are QM/MM models systematically improvable? A case study on carbonic anhydrase binding affinities.Journal of computer-aided molecular design · 2026Article
- Accurate and Time-Efficient Condensed-Phase Free Energy Simulations with Reaction Specific Δ-Machine Learning Potentials in CHARMM.Journal of chemical theory and computation · 2026Article
- Article
- QuantumPDB: A Workflow for High-Throughput Quantum Cluster Model Generation from Protein Structures.Journal of chemical information and modeling · 2026Article
- Multiscale machine learning molecular mechanics for mechanism and stereoselectivity of Diels-Alderase catalysis.Nature communications · 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
- Systematically Improvable and Locality Accelerated Enzymatic Reactivity Modeling: Toward Chemical Accuracy at Affordable Cost.Journal of chemical theory and computation · 2026Article
- Ligand-Induced Electronic Response Enables Predictive QM/MM Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effective Quantum Theory of EXAFS in a Dissipative Liquid-Phase Medium.The journal of physical chemistry. B · 2026Article
- Redefining Computational Enzymology with Multiscale Machine Learning/Molecular Mechanics: Catalytic Mechanism and Stereoselectivity in Diels-Alderases.Research square · 2025Article
- 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
- 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
- Quick-and-Easy Validation of Protein-Ligand Binding Models Using Fragment-Based Semiempirical Quantum Chemistry.Journal of chemical information and modeling · 2025Article
- Machine Learning in Enhancing Protein Binding Sites Predictions - What Has Changed Since Then?Combinatorial chemistry & high throughput screening · 2025Review
- Relative cooperativity in neutral and charged molecular clusters using QM/MM calculations.The Journal of chemical physics · 2024Article
- The GlycineThe journal of physical chemistry. B · 2023Article
- Data-driven enzyme engineering to identify function-enhancing enzymes.Protein engineering, design & selection : PEDS · 2023Review
- Computational Insights into the Catalytic Mechanism of Is-PETase: An Enzyme Capable of Degrading Poly(ethylene) Terephthalate.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Optimizing the Calculation of Free Energy Differences in Nonequilibrium Work SQM/MM Switching Simulations.The journal of physical chemistry. B · 2022Article
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Abstract
Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations provide key insights into enzyme structure-function relationships. Numerous studies have demonstrated that large QM regions are needed to systematically converge ground state, zero temperature properties with electrostatic embedding QM/MM. However, it is not well known if ab initio QM/MM free energy simulations have this same dependence, in part due to the hundreds of thousands of energy evaluations required for free energy estimations that in turn limit QM region size. Here, we leverage recent advances in electronic structure efficiency and accuracy to carry out range-separated hybrid density functional theory free energy simulations in a representative methyltransferase. By studying 200 ps of ab initio QM/MM dynamics for each of five QM regions from minimal (64 atoms) to one-sixth of the protein (544 atoms), we identify critical differences between large and small QM region QM/MM in charge transfer between substrates and active site residues as well as in geometric structure and dynamics that coincide with differences in predicted free energy barriers. Distinct geometric and electronic structure features in the largest QM region indicate that important aspects of enzymatic rate enhancement in methyltransferases are identified with large-scale electronic structure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.