Systematic Quantum Mechanical Region Determination in QM/MM Simulation.

  title={Systematic Quantum Mechanical Region Determination in QM/MM Simulation.},
  author={Maria Karelina and Heather J. Kulik},
  journal={Journal of chemical theory and computation},
  volume={13 2},
  • M. Karelina, H. Kulik
  • Published 2 January 2017
  • Chemistry, Biology
  • Journal of chemical theory and computation
Hybrid quantum mechanical-molecular mechanical (QM/MM) simulations are widely used in enzyme simulation. Over ten convergence studies of QM/MM methods have revealed over the past several years that key energetic and structural properties approach asymptotic limits with only very large (ca. 500-1000 atom) QM regions. This slow convergence has been observed to be due in part to significant charge transfer between the core active site and the surrounding protein environment, which cannot be… 
Large-scale QM/MM free energy simulations of enzyme catalysis reveal the influence of charge transfer.
  • H. Kulik
  • Physics, Chemistry
    Physical chemistry chemical physics : PCCP
  • 2018
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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While QM/MM studies of enzymatic reactions are widely used in computational chemistry, the results of such studies are subject to numerous sources of uncertainty, and the effect of different choices
Revealing quantum mechanical effects in enzyme catalysis with large-scale electronic structure simulation.
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Electronic Structure Topology Associated Domain and Its Physical Implication to Minimize Hybrid QM/MM Boundary Charge Transfer Effects
The charge transfer effect is an important component in the physical description of realistic proteins. In the hybrid quantum mechanical-molecular mechanical (QM/MM) simulations, the significant
Electronic Structure Topology Associated Domain is Useful to Minimize the Uncertainty of QM/MM Boundary Charge Transfer Effects
The charge transfer effect is an important component in the physical description of realistic proteins. In the hybrid quantum mechanical-molecular mechanical (QM/MM) simulations, the significant
Using Atomic Confining Potentials for Geometry Optimization and Vibrational Frequency Calculations in Quantum-Chemical Models of Enzyme Active Sites.
A simple alternative is introduced in which terminal atoms of the model system are placed in soft harmonic confining potentials rather than being rigidly constrained, which is more efficient for optimizing minima and transition states, as compared to the use of fixed-atom constraints, and also more robust against unwanted imaginary frequencies.


Evaluating boundary dependent errors in QM/MM simulations.
These errors demonstrate that the results of QM/MM calculations are heavily affected by the definition of the QM region (not only its size), and a convergence test is proposed to be a part of setting up Qm/MM simulations.
Accurate Reaction Energies in Proteins Obtained by Combining QM/MM and Large QM Calculations.
We here suggest and test a new method to obtain stable energies in proteins for charge-neutral reactions by running large quantum mechanical (QM) calculations on structures obtained by combined QM
How Large Should the QM Region Be in QM/MM Calculations? The Case of Catechol O-Methyltransferase
This work introduces charge shift analysis that reveals the minimum number of protein residues needed for quantitative agreement with large-QM simulations, and provides a recipe for a more careful determination of QM region sizes in future QM/MM studies of enzymes.
Do quantum mechanical energies calculated for small models of protein-active sites converge?
This paper discusses how the residues included in the QM model should be selected and how many residues need to be included before reaction energies converge, and shows that it is not a good approach to add groups according to their distance to the active site.
A pseudobond approach to combining quantum mechanical and molecular mechanical methods
A major challenge for combined quantum mechanical and molecular mechanical methods (QM/MM) to study large molecules is how to treat the QM/MM boundary that bisects some covalent bonds. Here a
Convergence in the QM‐only and QM/MM modeling of enzymatic reactions: A case study for acetylene hydratase
In the case of acetylene hydratase, a model with 408 QM atoms thus seems sufficient to achieve convergence in the computed relative energies to within 1–2 kcal/mol, and rather small variations in the relative energies from single‐point QM‐only and QM/MM calculations.
On the Convergence of QM/MM Energies.
In general, QM/MM calculations converge faster with system size than pure QM calculations, and there is little gain from correction schemes that are sensitive to the charge-redistribution scheme and may cause large errors if charges are close to the junctions.
A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations
A combined quantum mechanical (QM) and molecular mechanical (MM) potential has been developed for the study of reactions in condensed phases. For the quantum mechanical calculations semiempirical
A convergence study of QM/MM isomerization energies with the selected size of the QM region for peptidic systems.
A systematic study of the convergence of QM/MM results with respect to the chosen size of the QM region is presented for two examples of peptidic systems, showing that for the considered proton-transfer energy the Qm/MM treatment leads to a significantly faster convergence than the pure QM treatment.
Towards accurate ab initio QM/MM calculations of free-energy profiles of enzymatic reactions.
This work presents a way to evaluate the complete QM/MM activation free energy with an equal footing treatment of the solute and the solvent, and allows one to explore consistently various mechanistic and catalytic proposals while using ab initio (ai) Qm/MM approaches.