Computational Investigations of Organic Reaction Mechanisms

Jorgensen, William L.; Blake, James F.; Madura, Jeffry D.; Wierschke, Scott D.

doi:10.1021/bk-1987-0353.ch012

Cited by 14 publications

(9 citation statements)

References 13 publications

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“…They estimated a loss in equilibrium solvation energy of 23 kcal/mol on proceeding from reactants to the transition state, which led to good agreement with experiment. Later these studies were extended to OH -+ H 2 CO. 725 Continuum solvation models and molecular orbital-molecular mechanics 563,[567][568][569] methods go beyond these calculations in allowing the solute charge distribution to polarize in solution. The techniques are maturing, and this kind of calculation should become even more useful in the future.…”

Section: Classical Theory and Applicationmentioning

confidence: 99%

Current Status of Transition-State Theory

1996

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We present an overview of the current status of transition-state theory and its generalizations. We emphasize (i) recent improvements in available methodology for calculations on complex systems, including the interface with electronic structure theory, (ii) progress in the theory and application of transition-state theory to condensed-phase reactions, and (iii) insight into the relation of transition-state theory to accurate quantum dynamics and tests of its accuracy via comparisons with both experimental and other theoretical dynamical approximations.

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Section: Classical Theory and Applicationmentioning

confidence: 99%

Current Status of Transition-State Theory

1996

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“…To reliably simulate enzyme reactions, it is necessary to calculate the free energy change in a system of thousands of atoms, and considerable effort has been devoted to developing methods that correctly include the enzyme's free energy 26, 96–107. Reactions in liquids also involve a large number of atoms 108–112, but in many cases the solvent can be replaced by a homogeneous dielectric medium 43, 113–115, and this greatly simplifies the calculation. However, the large number of atoms is not the only difficulty.…”

Section: Complex Reactions In Liquids and Enzymesmentioning

confidence: 99%

Ensemble‐averaged variational transition state theory with optimized multidimensional tunneling for enzyme kinetics and other condensed‐phase reactions

Truhlar

Gao

Garcia‐Viloca

et al. 2004

Int J of Quantum Chemistry

124

207

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ABSTRACT:This paper provides an overview of a new method developed to include quantum mechanical effects and free energy sampling in calculations of reaction rates in enzymes. The paper includes an overview of variational transition state theory with optimized multidimensional tunneling for simple gas-phase reactions and then shows how this is extended to incorporate free energy effects and to include protein motions in the reaction coordinate by ensemble averaging. Finally we summarize recent comparisons to experiment for primary and secondary kinetic isotope effects for proton and hydride transfer reactions catalyzed by enzymes.

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“…This "geometric mapping" approach, which is akin to studying gas phase reactions through reaction path calculations, has been successfully applied to numerous organic reactions in solution. 54 Nevertheless, there is concern in this type of simulations because the solvent reaction coordinate is not explicitly included in the definition of the reaction coordinate. 55 A recent simulation study of the proton transfer in [HO‚‚‚H‚‚‚OH]in water indicates that there is considerable difference in the qualitative appearance of the free energy profile and the height of the predicted free energy barrier if the solvent reaction coordinate is explicitly taken into account.…”

Section: Computational Detailsmentioning

confidence: 99%

An Ab Initio Molecular Orbital−Valence Bond (MOVB) Method for Simulating Chemical Reactions in Solution

2000

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A mixed molecular orbital and valence bond (MOVB) method for describing the potential energy surface of reactive systems has been developed and applied to a model proton transfer reaction in aqueous solution. The MOVB method is based on a block-localized wave function (BLW) approach for defining the diabatic electronic states. Then, a configuration interaction Hamiltonian is constructed using these diabatic states as the basis function. It was found that the electronic coupling energy is large with a value of about 30 kcal/mol for the H 3 N-H-NH 3 + system, whereas the predicted activation barrier is only 1.2 kcal/mol using the 3-21G basis set. The MOVB results are found to be in good accord with the corresponding ab initio Hartree-Fock calculations for the proton transfer process. We have also incorporated solvent effects into the MOVB Hamiltonian in the spirit of combined QM/MM calculations, and have modeled the proton transfer between ammonium ion and ammonia in water using Monte Carlo simulations. The potential of mean force was computed via free energy perturbation coupled with umbrella sampling techniques using (1) an energy gap mapping approach, and (2) a geometrical mapping procedure. Solvent effects increase the barrier height by about 2.2 kcal/mol from the MOVB and HF ground state potential energy surface. The present study demonstrated the feasibility of ab initio MOVB method for studying chemical reactions by incorporating explicit solvent effects in the description of the reaction coordinate in combined QM/MM simulations.

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Computational Investigations of Organic Reaction Mechanisms

Cited by 14 publications

References 13 publications

Current Status of Transition-State Theory

Current Status of Transition-State Theory

Ensemble‐averaged variational transition state theory with optimized multidimensional tunneling for enzyme kinetics and other condensed‐phase reactions

An Ab Initio Molecular Orbital−Valence Bond (MOVB) Method for Simulating Chemical Reactions in Solution

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