Quantum Mechanical Dynamical Effects in an Enzyme-Catalyzed Proton Transfer Reaction

Alhambra, Cristóbal; Gao, Jiali; Corchado, J. C.; Villà, Jordi; Truhlar, Donald G.

doi:10.1021/ja9831655

Cited by 136 publications

(180 citation statements)

References 58 publications

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“…32,97,114,123,128,130,139,141 In general, it should be more reliable to use a method that incorporates protein fluctuations and free energy simulations, such as sampling ensemble members from a transition state ensemble identified by a maximum in a PMF profile.…”

Section: Methods Based On a Single Reaction Pathmentioning

confidence: 99%

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

2006

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Section: Methods Based On a Single Reaction Pathmentioning

confidence: 99%

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

2006

Self Cite

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“…Enolase has been simulated by both semiempirical and ab initio QM/MM methods [123,15]. Chorismate mutase catalyzes the Claisen rearrangement from chorismate to prephenate.…”

Section: Applications Of Ab Initio Qm/mm Methodsmentioning

confidence: 99%

Free Energies of Chemical Reactions in Solution and in Enzymes with Ab Initio Quantum Mechanics/Molecular Mechanics Methods

Yang

2008

Annu. Rev. Phys. Chem.

417

401

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Combined QM/MM methods provide an accurate and efficient energetic description of complex chemical and biological systems, leading to significant advances in the understanding of chemical reactions in solution and in enzymes. Progress in QM/MM methodology and application will be reviewed, with a focus on ab initio QM based approaches. Ab initio QM/MM methods capitalize on the accuracy and reliability of the associated quantum mechanical approaches, however at a much higher computational cost compared with semiempirical quantum mechanical approaches. Thus reaction path and activation free energy calculations based on ab initio QM/MM methods encounter unique challenges in simulation timescales and phase space sampling. Recent developments overcoming these challenges and enabling accurate free energy determination for reaction processes in solution and enzymes will be featured in this review, along with applications.

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“…One method that has been successfully introduced to computational enzymology is the ensembleaveraged variational transition-state theory with QM/MM sampling (EA-VTST-QM/MM), which has been applied to a number of enzyme systems. 2,3,[9][10][11][12][13] Both primary and secondary KIEs can be computed using the EA-VTST-QM/ MM method, and the method includes contributions of multidimensional tunneling. In another work, a grid-based hybrid approach was used to model quantum effects in hydrogen transfer reactions by numerically solving the vibrational wavefunction of the transferring hydrogen nucleus.…”

Section: Introductionmentioning

confidence: 99%

An Integrated Path Integral and Free-Energy Perturbation−Umbrella Sampling Method for Computing Kinetic Isotope Effects of Chemical Reactions in Solution and in Enzymes

Major

Gao

2007

J. Chem. Theory Comput.

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234

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An integrated centroid path integral and free-energy perturbation-umbrella sampling (PI-FEP/UM) method for computing kinetic isotope effects (KIEs) for chemical reactions in solution and in enzymes is presented. The method is based on the bisection quantized classical path sampling in centroid path integral simulations to include nuclear quantum corrections in the classical potential of mean force. The required accuracy for computing kinetic isotope effects is achieved by coupled free-energy perturbation and umbrella sampling for reactions involving different isotopes. The use of FEP results in relatively small statistical uncertainties, whereas if kinetic isotope effects are computed directly by the difference in free energies obtained from the quantum mechanical potentials of mean force for different isotopes, the statistical errors are significantly greater. The PI-FEP/UM method is illustrated in two applications. The first reaction is the decarboxylation of N-methyl picolinate in water, and the primary 13 C and secondary 15 N KIEs have been determined. The second reaction is the proton-transfer reaction between nitroethane and acetate ions in water, and the total kinetic isotope effects were obtained. In both cases, the computational results are in accord with experimental results, and the findings provide further insight into the mechanism of these reactions in water.

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Quantum Mechanical Dynamical Effects in an Enzyme-Catalyzed Proton Transfer Reaction

Cited by 136 publications

References 58 publications

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

Multidimensional Tunneling, Recrossing, and the Transmission Coefficient for Enzymatic Reactions

Free Energies of Chemical Reactions in Solution and in Enzymes with Ab Initio Quantum Mechanics/Molecular Mechanics Methods

An Integrated Path Integral and Free-Energy Perturbation−Umbrella Sampling Method for Computing Kinetic Isotope Effects of Chemical Reactions in Solution and in Enzymes

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