Q<scp>UANTUM</scp>M<scp>ECHANICAL</scp>M<scp>ETHODS FOR</scp>E<scp>NZYME</scp>K<scp>INETICS</scp>

Gao, Jiali; Truhlar, Donald G.

doi:10.1146/annurev.physchem.53.091301.150114

Cited by 770 publications

(656 citation statements)

References 275 publications

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“…As in classical TST, the PMF, w(z), can be computed from the equilibrium average without any dynamical information, and it is defined by (5) where z R is the minimum point at the reactant state in the PMF and the ensemble average < ··· > is obtained by the effective potential of eq. (2).…”

Section: Theoretical Background Path Integral Quantum Mechanical Ratementioning

confidence: 99%

“…These results are close to the semiclassical limit, suggesting that tunneling contributions are not significant for this reaction in aqueous solution. To assess the tunneling contributions, we have used the multidimensional tunneling (MT) algorithm developed by Truhlar and coworkers, 9 extended to enzyme applications in the EA-VTST method, 5,6 to determine the average tunneling transmission factor, yielding a value of 〈κ〉 = 1.3 using the present potential. 30 This suggests that tunneling only makes minor contributions in the present case for the aqueous reaction.…”

Section: Swain-schaad Exponentsmentioning

confidence: 99%

“…3,4 Quantum mechanics is essential for computing KIEs of reactions in solutions and in enzymes. 5,6 First, electronic structural theory is required to adequately describe the potential energy surface for bond forming and breaking processes. Secondly, nuclear quantum effects including both quantized vibration and tunneling are needed to obtain accurate rate constants.…”

Section: Introductionmentioning

confidence: 99%

“…9 In principle, these techniques can be directly extended to condensed phase systems; however, the size and complexity of these systems often make it intractable computationally. One method that has been successfully introduced to the study of enzyme reaction rates is the ensemble-averaged variational transition state theory with QM/MM sampling (EA-VTST-QM/ MM), 5,6 which has been applied to a number of enzyme systems. This technique includes multidimensional tunneling.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Theoretical Background Path Integral Quantum Mechanical Ratementioning

confidence: 99%

Section: Swain-schaad Exponentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Under some conditions, such as high temperature, extremes of pH or mechanical forces, protein will unfold into random coil that loses biochemical function (Selkoe 2003). Since folding and unfolding are essential to life, literatures on the study of these processes are very rich (Gao and Truhlar 2002;Gao et al 2006;Freddolino et al 2010;Yang et al 2010;Alhambra et al 2000;Duan et al 2010;Shank et al 2010). And it has been greatly advanced in recent years by the development of fast time-resolved techniques.…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

Zhao

Cheng

2011

Amino Acids

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Steered molecular dynamics simulations are performed to explore the unfolding and refolding processes of CLN025, a 10-residue beta-hairpin. In unfolding process, when CLN025 is pulled along the termini, the forceextension curve goes back and forth between negative and positive values not long after the beginning of simulation. That is so different from what happens in other peptides, where force is positive most of the time. The abnormal phenomenon indicates that electrostatic interaction between the charged termini plays an important role in the stability of the beta-hairpin. In the refolding process, the collapse to beta-hairpin-like conformations is very fast, within only 3.6 ns, which is driven by hydrophobic interactions at the termini, as the hydrophobic cluster involves aromatic rings of Tyr1, Tyr2, Trp9, and Tyr10. Our simulations improve the understanding on the structure and function of this type of miniprotein and will be helpful to further investigate the unfolding and refolding of more complex proteins.

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Quantum Mechanical/Molecular Mechanical ( QM / MM ) Methods and Applictions in Bioinorganic Chemistry

Ryde¹

2005

Encyclopedia of Inorganic Chemistry

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The combination of quantum mechanics and molecular mechanics (QM/MM) methods is a promising approach to study the structure, function, and properties of proteins. The number of QM/MM applications on metalloproteins has been steadily increasing and it is the method of choice to study the influence of the protein onto the structure, spectroscopy, and energetics of an active site. In particular, it has been shown that QM/MM calculations can provide geometries of metal sites in proteins with an accuracy that is better than in low‐ and medium‐resolution crystal structures. However, it is quite hard to obtain reliable and converged energies. Therefore, QM/MM is still an area of method development and no consensus of the best treatment of a protein has yet been reached. This review covers various aspects of QM/MM studies of metalloproteins, including methods to incorporate experimental data in the calculations, methods to obtain reliable energies, as well as some examples of typical applications.

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QUANTUMMECHANICALMETHODS FORENZYMEKINETICS

Cited by 770 publications

References 275 publications

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

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

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

Quantum Mechanical/Molecular Mechanical ( QM / MM ) Methods and Applictions in Bioinorganic Chemistry

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