Simulations of quantum mechanical corrections for rate constants of hydride-transfer reactions in enzymes and solutions

Hwang, Jiann Yang; Chu, Zhen T.; Yadav, Anil Kumar; Warshel, Arieh

doi:10.1021/j100175a009

Cited by 188 publications

(208 citation statements)

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“…18,19 From eq 9, the quantum mechanical potential of mean force, defined as a function of the centroid reaction coordinate, z j, can readily be expressed as follows:…”

Section: The Quantized Classical Path (Qcp) Methodmentioning

confidence: 99%

“…14,15 The method yielded good results for primary KIEs as it was applied to several hydride transfer reactions, 16 although the authors noted that a major limitation is its complexity, preventing it from extending to quantizing more than one particle. 17 The third technique, which was among the first applications to incorporate nuclear quantum effects in enzyme reactions, is the quantized classical path (QCP) method developed by Hwang et al [18][19][20] The discrete Feynman path integral method 21 has been used in a variety of applications since it offers an efficient and general approach for treating nuclear quantum effects in condensed-phase simulations. 20,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Here, we focus on applications to biomolecular systems.…”

Section: Introductionmentioning

confidence: 99%

“…The QCP method is also based on centroid path integral sampling, but it is formulated as a correction to the classical potential of mean force (PMF) from molecular dynamics simulations. 18,19,23 Thus, the classical simulations and quantum corrections are fully separated, making it particularly attractive and efficient to model enzymatic reactions. Unfortunately, the QCP method has not been widely used, and it is very difficult to obtain converged results using "standard" sampling schemes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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.

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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“…18,19 From eq 9, the quantum mechanical potential of mean force, defined as a function of the centroid reaction coordinate, z j, can readily be expressed as follows:…”

Section: The Quantized Classical Path (Qcp) Methodmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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.

234

View full text Add to dashboard Cite

show abstract

“…An alternative procedure is to carry out classical molecular dynamics simulations first, followed by centroid path integral simulations to determine the quantum effects. Sprik et al 15 explored this idea to estimate quantum effects for an electron in a lattice matrix of hard spheres, whereas Warshel and coworkers [23][24][25][26] employed a quantized classical path (QCP) method in several applications to determine quantum effects along a reaction path. In the QCP method, the classical potential of mean force (PMF) is obtained first, followed by estimating quantum contributions to the free energy of activation.…”

Section: Introductionmentioning

confidence: 99%

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

2007

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An integrated Feynman path integral-free energy perturbation and umbrella sampling (PI-FEP/UM) method has been used to investigate the kinetic isotope effects (KIEs) in the proton transfer reaction between nitroethane and acetate ion in water. In the present study, both nuclear and electronic quantum effects are explicitly treated for the reacting system. The nuclear quantum effects are represented by bisection sampling centroid path integral simulations, while the potential energy surface is described by a combined quantum mechanical and molecular mechanical (QM/MM) potential. The accuracy essential for computing KIEs is achieved by a FEP technique that transforms the mass of a light isotope into a heavy one, which is equivalent to the perturbation of the coordinates for the path integral quasiparticle in the bisection sampling scheme. The PI-FEP/UM method is applied to the proton abstraction of nitroethane by acetate ion in water through molecular dynamics simulations. The rule of the geometric mean and the Swain-Schaad exponents for various isotopic substitutions at the primary and secondary sites have been examined. The computed total deuterium KIEs are in accord with experiments. It is found that the mixed isotopic Swain-Schaad exponents are very close to the semiclassical limits, suggesting that tunneling effects do not significantly affect this property for the reaction between nitroethane and acetate ion in aqueous solution.

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“…These include, e.g., approaches based on other quantum transition state theories [18,19] or on the quantized classical path method [5,20,21].…”

Section: Kinetic Isotope Effectsmentioning

confidence: 99%

Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene

Zimmermann

Vaníček

2010

J Mol Model

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Simulations of quantum mechanical corrections for rate constants of hydride-transfer reactions in enzymes and solutions

Cited by 188 publications

References 0 publications

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

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

Combined QM/MM and path integral simulations of kinetic isotope effects in the proton transfer reaction between nitroethane and acetate ion in water

Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene

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