Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase

Narin Lawan; Kara E. Ranaghan; Frederick R. Manby; Adrian J. Mulholland

doi:10.1016/j.cplett.2014.06.010

Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase

Narin Lawan, Kara E. Ranaghan, Frederick R. Manby, Adrian J. Mulholland^*

^*Corresponding author for this work

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Abstract

Quantum mechanics/molecular mechanics (QM/MM) methods are a popular tool in the investigation of enzyme reactions. Here, we compare B3LYP density functional theory (DFT) and ab initio QM/MM methods for modelling the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate in chorismate synthase. Good agreement with experimental data is only obtained at the SCS-MP2/CHARMM27 level for a reaction mechanism in which phosphate elimination precedes proton transfer. B3LYP predicts reaction energetics that are qualitatively wrong, stressing the need for ab initio QM/MM methods, and caution in interpretation of DFT results for this enzyme.

Original language	English
Pages (from-to)	380-385
Number of pages	6
Journal	Chemical Physics Letters
Volume	608
DOIs	https://doi.org/10.1016/j.cplett.2014.06.010
Publication status	Published - 21 Jul 2014

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cited By 2

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Physical & Theoretical

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title = "Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase",

abstract = "Quantum mechanics/molecular mechanics (QM/MM) methods are a popular tool in the investigation of enzyme reactions. Here, we compare B3LYP density functional theory (DFT) and ab initio QM/MM methods for modelling the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate in chorismate synthase. Good agreement with experimental data is only obtained at the SCS-MP2/CHARMM27 level for a reaction mechanism in which phosphate elimination precedes proton transfer. B3LYP predicts reaction energetics that are qualitatively wrong, stressing the need for ab initio QM/MM methods, and caution in interpretation of DFT results for this enzyme.",

author = "Narin Lawan and Ranaghan, \{Kara E.\} and Manby, \{Frederick R.\} and Mulholland, \{Adrian J.\}",

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AU - Ranaghan, Kara E.

AU - Manby, Frederick R.

AU - Mulholland, Adrian J.

N1 - cited By 2

PY - 2014/7/21

Y1 - 2014/7/21

N2 - Quantum mechanics/molecular mechanics (QM/MM) methods are a popular tool in the investigation of enzyme reactions. Here, we compare B3LYP density functional theory (DFT) and ab initio QM/MM methods for modelling the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate in chorismate synthase. Good agreement with experimental data is only obtained at the SCS-MP2/CHARMM27 level for a reaction mechanism in which phosphate elimination precedes proton transfer. B3LYP predicts reaction energetics that are qualitatively wrong, stressing the need for ab initio QM/MM methods, and caution in interpretation of DFT results for this enzyme.

AB - Quantum mechanics/molecular mechanics (QM/MM) methods are a popular tool in the investigation of enzyme reactions. Here, we compare B3LYP density functional theory (DFT) and ab initio QM/MM methods for modelling the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate in chorismate synthase. Good agreement with experimental data is only obtained at the SCS-MP2/CHARMM27 level for a reaction mechanism in which phosphate elimination precedes proton transfer. B3LYP predicts reaction energetics that are qualitatively wrong, stressing the need for ab initio QM/MM methods, and caution in interpretation of DFT results for this enzyme.

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U2 - 10.1016/j.cplett.2014.06.010

DO - 10.1016/j.cplett.2014.06.010

M3 - Article (Academic Journal)

SN - 0009-2614

VL - 608

SP - 380

EP - 385

JO - Chemical Physics Letters

JF - Chemical Physics Letters

ER -

Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase

Abstract

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Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation

COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

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Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase

Abstract

Bibliographical note

Research Groups and Themes

Access to Document

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Fingerprint

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Computational tools for enzyme engineering: bridging the gap between enzymologists and expert simulation

COMPUTATIONAL BIOCHEMISTRY: PREDICTIVE MODELLING FOR BIOLOGY AND MEDICINE

Cite this