scholarly journals Application of Q2MM to predictions in stereoselective synthesis

2018 ◽  
Vol 54 (60) ◽  
pp. 8294-8311 ◽  
Author(s):  
Anthony R. Rosales ◽  
Taylor R. Quinn ◽  
Jessica Wahlers ◽  
Anna Tomberg ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Transition State ◽  
Molecular Mechanics ◽  
Stereoselective Synthesis ◽  
Force Fields ◽  
Accurate Prediction ◽  
State Force

Transition state force fields derived by Quantum Guided Molecular Mechanics (Q2MM) allows the rapid and accurate prediction of stereoselectivity.

Model Calculations of Isotope Effects. III. Isotope Effects in Hydrogen Transfer Reactions, and Transition State Force Fields

1979 ◽  
Vol 32 (9) ◽  
pp. 1869
Author(s):  
DJ McLennan
Keyword(s):  
Transition State ◽  
Hydrogen Transfer ◽  
Force Fields ◽  
Isotope Effects ◽  
Semiempirical Method ◽  
Model Calculations ◽  
Surface Hydrogen ◽  
Kinetic Isotope ◽  
State Force ◽  
Better Than

Model calculations of kinetic isotope effects for the reactions: C2H6+·CH3 → ·C2H5+CH4 CH4 + ·CF3 → ·CH3+CHF3 are reported. Transition state geometries were those calculated by Dewar and coworkers using the MNDO semiempirical method. Transition state force fields were formulated from empirical expressions for stretching, bending, linear bending and interaction valence force constants by using bond orders as disposable parameters. Although it proved impossible to assign a best force field to either reaction, the calculated isotope effects generally were in satisfactory agreement with experiment, and were better than those calculated from the MNDO potential energy surface. Hydrogen tunnelling is apparently implicated in the CH4+ CF3 reaction.

scholarly journals Automated Fitting of Transition State Force Fields for Biomolecular Simulations

2020 ◽  
Author(s):  
Olaf Wiest ◽  
Taylor R. Quinn ◽  
Himani Patel ◽  
Paul Helquist ◽  
Per-Ola Norrby ◽  
...  
Keyword(s):  
Transition State ◽  
Force Field ◽  
Molecular Mechanics ◽  
Small Molecule ◽  
Functional Form ◽  
Enzymatic Reactions ◽  
Hmgcoa Reductase ◽  
Biomolecular Simulations ◽  
Pseudomonas Mevalonii ◽  
State Force

The application of the Quantum Guided Molecular Mechanics (Q2MM) method to transition states of enzymatic reactions to generate a transition state force field (TSFF) with the functional form of AMBER. The differences to fitting of small-molecule TSFFs and the similarities of the approach to transfer learning are discussed. The application to the transition state of the second hydride transfer in HMGCoA Reductase from Pseudomonas mevalonii is discussed. <br><br>

scholarly journals Proofreading experimentally assigned stereochemistry through Q2MM predictions in Pd-catalyzed allylic aminations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessica Wahlers ◽  
Jèssica Margalef ◽  
Eric Hansen ◽  
Armita Bayesteh ◽  
Paul Helquist ◽  
...  
Keyword(s):  
Transition State ◽  
Force Field ◽  
Molecular Mechanics ◽  
Bioactive Compounds ◽  
Palladium Catalyzed ◽  
The One ◽  
Nitrogen Nucleophiles ◽  
State Force ◽  
Selection Of

AbstractThe palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.

scholarly journals Proofreading Experimentally Assigned Stereochemistry Through Q2MM Predictions in Pd-Catalyzed Allylic Aminations

2021 ◽  
Author(s):  
Jessica Wahlers ◽  
Jessica Margalef ◽  
Eric Hansen ◽  
Armita Bayesteh ◽  
Paul Helquist ◽  
...  
Keyword(s):  
Transition State ◽  
Force Field ◽  
Molecular Mechanics ◽  
Bioactive Compounds ◽  
Palladium Catalyzed ◽  
The One ◽  
Nitrogen Nucleophiles ◽  
State Force ◽  
Selection Of

Abstract The palladium-catalyzed enantioselective allylic substitution by carbon or nitrogen nucleophiles is a key transformation that is particularly useful for the synthesis of bioactive compounds. Unfortunately, the selection of a suitable ligand/substrate combination often requires significant screening effort. Here, we show that a transition state force field (TSFF) derived by the quantum-guided molecular mechanics (Q2MM) method can be used to rapidly screen ligand/substrate combinations. Testing of this method on 77 literature reactions revealed several cases where the computationally predicted major enantiomer differed from the one reported. Interestingly, experimental follow-up led to a reassignment of the experimentally observed configuration. This result demonstrates the power of mechanistically based methods to predict and, where necessary, correct the stereochemical outcome.

scholarly journals Automated Fitting of Transition State Force Fields for Biomolecular Simulations

2020 ◽  
Author(s):  
Olaf Wiest ◽  
Taylor R. Quinn ◽  
Himani Patel ◽  
Paul Helquist ◽  
Per-Ola Norrby ◽  
...  
Keyword(s):  
Transition State ◽  
Force Field ◽  
Molecular Mechanics ◽  
Small Molecule ◽  
Functional Form ◽  
Enzymatic Reactions ◽  
Hmgcoa Reductase ◽  
Biomolecular Simulations ◽  
Pseudomonas Mevalonii ◽  
State Force

The application of the Quantum Guided Molecular Mechanics (Q2MM) method to transition states of enzymatic reactions to generate a transition state force field (TSFF) with the functional form of AMBER. The differences to fitting of small-molecule TSFFs and the similarities of the approach to transfer learning are discussed. The application to the transition state of the second hydride transfer in HMGCoA Reductase from Pseudomonas mevalonii is discussed. <br><br>

Automated Parametrization of Biomolecular Force Fields from Quantum Mechanics/Molecular Mechanics (QM/MM) Simulations through Force Matching

2007 ◽  
Vol 3 (2) ◽  
pp. 628-639 ◽  
Author(s):  
Patrick Maurer ◽  
Alessandro Laio ◽  
Håkan W. Hugosson ◽  
Maria Carola Colombo ◽  
Ursula Rothlisberger
Keyword(s):  
Quantum Mechanics ◽  
Molecular Mechanics ◽  
Force Fields ◽  
Force Matching
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