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

Kamerlin, Shina Caroline Lynn; Harańczyk, Maciej; Warshel, Arieh

doi:10.1002/cphc.200800753

Cited by 88 publications

(125 citation statements)

References 79 publications

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“…However, as was demonstrated in Ref. 20 , calculations involving mixed implicit/explicit solvent are problematic, with the inclusion of extra water molecules being likely to model was a conscious one, and is in line with our previous work.…”

Section: Ii2 Computational Detailssupporting

confidence: 89%

“…The choice of COSMO rather than PCM for the corrected energies was due to the fact that our validation study in the case of phosphate diesters 17 shows that this model is able to effectively screen charge-charge interactions and provide reasonable solvation free energies. Additionally, this approach has been successful in our previous studies of phosphoryl transfer 17,20,21,24,57 . Finally, in all cases, the UFF model was used rather than the standard UA0 model.…”

Section: Ii2 Computational Detailsmentioning

confidence: 91%

“…The author thanks the Swedish Research Council (VR, grant 2010-5026) for funding, as well as the PDC center for High Performance Computing at KTH and the National Supercomputer Center (NSC) at Linköping University for access to computational resources (SNIC grants 001/11-12 and 001/ [11][12][13][14][15][16][17][18][19][20] …”

Section: Acknowledgementsmentioning

confidence: 99%

“…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%

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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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Section: Ii2 Computational Detailssupporting

confidence: 89%

Section: Ii2 Computational Detailsmentioning

confidence: 91%

Section: Acknowledgementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Implicit solvent models are commonly used at all levels of molecular granularity, from QM (Refs. [24][25][26][27] and polarizable methods [28][29][30] to MM forcefields. [31][32][33][34] Unsurprisingly, lower resolution forcefields and solvent models often incur penalties on accuracy and require the development a) Author to whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

A smoothly decoupled particle interface: New methods for coupling explicit and implicit solvent

Wagoner

Pande

2011

The Journal of Chemical Physics

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A common theme of studies using molecular simulation is a necessary compromise between computational efficiency and resolution of the forcefield that is used. Significant efforts have been directed at combining multiple levels of granularity within a single simulation in order to maintain the efficiency of coarse-grained models, while using finer resolution in regions where such details are expected to play an important role. A specific example of this paradigm is the development of hybrid solvent models, which explicitly sample the solvent degrees of freedom within a specified domain while utilizing a continuum description elsewhere. Unfortunately, these models are complicated by the presence of structural artifacts at or near the explicit/implicit boundary. The presence of these artifacts significantly complicates the use of such models, both undermining the accuracy obtained and necessitating the parameterization of effective potentials to counteract the artificial interactions. In this work, we introduce a novel hybrid solvent model that employs a smoothly decoupled particle interface (SDPI), a switching region that gradually transitions from fully interacting particles to a continuum solvent. The resulting SDPI model allows for the use of an implicit solvent model based on a simple theory that needs to only reproduce the behavior of bulk solvent rather than the more complex features of local interactions. In this study, the SDPI model is tested on spherical hybrid domains using a coarse-grained representation of water that includes only Lennard-Jones interactions. The results demonstrate that this model is capable of reproducing solvent configurations absent of boundary artifacts, as if they were taken from full explicit simulations.

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Nanochemie: Mirkin ausgezeichnet / Biochemie: Shokat geehrt / Theorie: Warshel gewählt

2009

Angewandte Chemie

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

Cited by 88 publications

References 79 publications

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

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

A smoothly decoupled particle interface: New methods for coupling explicit and implicit solvent

Nanochemie: Mirkin ausgezeichnet / Biochemie: Shokat geehrt / Theorie: Warshel gewählt

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