Theoretical Studies of the Hydrolysis of the Methyl Phosphate Anion

Hu, Ching Han; Brinck, Tore

doi:10.1021/jp9835061

Cited by 101 publications

(155 citation statements)

References 33 publications

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“…The reaction dataset includes reaction energies, barrier heights, and relative energies of intermediates for over 19 associative reactions and 3 dissociative reactions. Note that although these reactions cover a fairly broad range of mechanisms in the gas phase, they do not consider more complex reaction mechanisms that may occur in the aqueous phase, such as water-assisted pathways 37,118,119 or complex water relays. 120 These mechanisms often require fairly sophisticated transition path sampling techniques 121,122 and sometimes intricate bridging water chains that are currently not amenable to efficient automated parameter optimization.…”

Section: Geometriesmentioning

confidence: 99%

Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions: H, O, and P Atoms

Nam

Cui

Gao

et al. 2007

J. Chem. Theory Comput.

196

355

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Abstract:A semiempirical AM1/d Hamiltonian is developed to model phosphoryl transfer reactions catalyzed by enzymes and ribozymes for use in linear-scaling calculations and combined quantum mechanical/molecular mechanical simulations. The model, designated AM1/d-PhoT, is parametrized for H, O, and P atoms to reproduce high-level density-functional results from a recently constructed database of quantum calculations for RNA catalysis (http://theory.chem.umn.edu/Database/QCRNA), including geometries and relative energies of minima, transition states and reactive intermediates, dipole moments, proton affinities, and other relevant properties. The model is tested in the gas phase and in solution using a QM/MM potential. The results indicate that the method provides significantly higher accuracy than MNDO/ d, AM1, and PM3 methods and, for the transphosphorylation reactions, is in close agreement with the density-functional calculations at the B3LYP/6-311++G(3df,2p) level with a reduction in computational cost of 3-4 orders of magnitude. The model is expected to have considerable impact on the application of semiempirical QM/MM methods to transphosphorylation reactions in solution, enzymes, and ribozymes and to ultimately facilitate the design of improved nextgeneration multiscale quantum models.

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Section: Geometriesmentioning

confidence: 99%

Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions: H, O, and P Atoms

Nam

Cui

Gao

et al. 2007

J. Chem. Theory Comput.

196

355

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show abstract

“…As a result, phosphate esters have been the subject of extensive experimental 3,6-13 and theoretical [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] studies (though the precise mechanisms of both the solution and enzyme catalyzed reactions remain controversial, see e.g. [6][7][8]12,14,15,25,26,29,[33][34][35] ).…”

Section: Introductionmentioning

confidence: 99%

Theoretical Comparison ofp-Nitrophenyl Phosphate and Sulfate Hydrolysis in Aqueous Solution: Implications for Enzyme-Catalyzed Sulfuryl Transfer

Kamerlin

2011

J. Org. Chem.

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Both phosphoryl and sulfuryl transfer are ubiquitous in biology, being involved in a wide range of processes, ranging from cell division to apoptosis. Additionally, it is becoming increasingly clear that enzymes that can catalyze phosphoryl transfer can often cross-catalyze sulfuryl-transfer (and vice versa).However, while there have been extensive experimental and theoretical studies performed on phosphoryl transfer, the body of available research on sulfuryl transfer is comparatively much smaller.The present work presents a direct theoretical comparison of p-nitrophenyl phosphate and sulfate monoester hydrolysis, both of which are considered prototype systems for probing phosphoryl and sulfuryl transfer respectively. Specifically, free energy surfaces have been generated using density functional theory, by initial geometry optimization in PCM using the 6-31+G* basis set and the B3LYP density functional, followed by single point calculations using the larger 6-311+G** basis set and the COSMO continuum model. The resulting surfaces have been then used to identify the relevant transition states, either by further unconstrained geometry optimization, or from the surface itself where possible.Additionally, configurational entropies were evaluated using a combination of the quasiharmonic approximation and the restraint release approach and added to the calculated activation barriers as a correction. Finally, the overall activation entropy was estimated by approximating the solvent contribution to the total activation entropy using the Langevin dipoles solvation model. We have reproduced both the experimentally observed activation barriers and the observed trend in the activation entropies with reasonable accuracy, as well providing a comparison of calculated and observed 15 N and 18 O kinetic isotope effects. We demonstrate that, counterintuitively, the hydrolysis of the p-nitrophenyl sulfate proceeds through a more expa show that the solvation effects upon moving from the ground state to the transition state are quite different for both reactions, suggesting that the enzymes that catalyze these reactions would need active 4 sites with quite different electrostatic preorganization for the efficient catalysis of either reaction (despite which many enzymes can catalyze both phosphoryl and sulfuryl transfer). We believe that such a comparative study is an important foundation for understanding the molecular basis for phosphatesulfate cross promiscuity within members of the alkaline phosphatase superfamily.

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“…Refs [40,48,49] for examples of the use of such an approach). This is a cause of concern, as there are several potential pitfalls with such an approach, even if one where to ignore the inherent problems associated with generating adequate free-energy surfaces for phosphate hydrolysis in the presence of explicit water molecules (and with subsequent transition state identification) [27,50] .…”

Section: Introductionmentioning

confidence: 99%

“…This situation becomes in turn more serious when one only uses a few water molecules immersed in a continuum model as was done in Refs. [40,48,49] . Here, the explicit water molecules are not likely to have the correct orientation of the corresponding molecules in an explicit infinite system.…”

Section: Introductionmentioning

confidence: 99%

Are Mixed Explicit/Implicit Solvation Models Reliable for Studying Phosphate Hydrolysis? A Comparative Study of Continuum, Explicit and Mixed Solvation Models

2009

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Theoretical Studies of the Hydrolysis of the Methyl Phosphate Anion

Cited by 101 publications

References 33 publications

Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions: H, O, and P Atoms

Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions: H, O, and P Atoms

Theoretical Comparison ofp-Nitrophenyl Phosphate and Sulfate Hydrolysis in Aqueous Solution: Implications for Enzyme-Catalyzed Sulfuryl Transfer

Are Mixed Explicit/Implicit Solvation Models Reliable for Studying Phosphate Hydrolysis? A Comparative Study of Continuum, Explicit and Mixed Solvation Models

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