A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase

We present a density functional theory (DFT) hybrid quantum mechanical/molecular mechanical (QM-MM) implementation developed for simulations of reactions in complex environments. It is particularly suited to study enzyme active sites or solutes in condensed phases. The method combines a QM descripti...

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Detalles Bibliográficos
Publicado: 2003
Materias:
Activation energy
Catalysis
Catalyst activity
Computer simulation
Molecular structure
Numerical analysis
Probability density function
Quantum theory
Chorismate mutase
Lennard-Jones potential interactions
Molecular mechanical scheme
Enzymes
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v107_n49_p13728_Crespo
http://hdl.handle.net/20.500.12110/paper_15206106_v107_n49_p13728_Crespo
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paper:paper_15206106_v107_n49_p13728_Crespo
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spelling paper:paper_15206106_v107_n49_p13728_Crespo2023-06-08T16:18:51Z A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase Activation energy Catalysis Catalyst activity Computer simulation Molecular structure Numerical analysis Probability density function Quantum theory Chorismate mutase Lennard-Jones potential interactions Molecular mechanical scheme Enzymes We present a density functional theory (DFT) hybrid quantum mechanical/molecular mechanical (QM-MM) implementation developed for simulations of reactions in complex environments. It is particularly suited to study enzyme active sites or solutes in condensed phases. The method combines a QM description of the solute with a MM treatment of the environment. The QM fragment is treated using DFT as implemented in the computationally efficient program SIESTA, while the environment is treated using the Wang et al. Amber force field parametrization. We applied our new QM-MM scheme to study the conversion of chorismate to prephenate by computing the reaction energy profile in vacuo, aqueous solution and in the active site of the B. subtilis chorismate mutase enzyme. We have performed calculations for two different choices of the QM subsystem in the enzyme simulations: including only the substrate moiety and the substrate plus the charged side chains glu78 and arg90, respectively. In both cases, our results are in good agreement with experiment. The catalytic activity achieved by chorismate mutase relative to the uncatalyzed reaction in solution is due to both a minor destabilization of the substrate molecule by compression and a major electrostatic stabilization of the transition state, which reduce the activation energy of the reaction. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v107_n49_p13728_Crespo http://hdl.handle.net/20.500.12110/paper_15206106_v107_n49_p13728_Crespo
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Activation energy
Catalysis
Catalyst activity
Computer simulation
Molecular structure
Numerical analysis
Probability density function
Quantum theory
Chorismate mutase
Lennard-Jones potential interactions
Molecular mechanical scheme
Enzymes
spellingShingle Activation energy
Catalysis
Catalyst activity
Computer simulation
Molecular structure
Numerical analysis
Probability density function
Quantum theory
Chorismate mutase
Lennard-Jones potential interactions
Molecular mechanical scheme
Enzymes
A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
topic_facet Activation energy
Catalysis
Catalyst activity
Computer simulation
Molecular structure
Numerical analysis
Probability density function
Quantum theory
Chorismate mutase
Lennard-Jones potential interactions
Molecular mechanical scheme
Enzymes
description We present a density functional theory (DFT) hybrid quantum mechanical/molecular mechanical (QM-MM) implementation developed for simulations of reactions in complex environments. It is particularly suited to study enzyme active sites or solutes in condensed phases. The method combines a QM description of the solute with a MM treatment of the environment. The QM fragment is treated using DFT as implemented in the computationally efficient program SIESTA, while the environment is treated using the Wang et al. Amber force field parametrization. We applied our new QM-MM scheme to study the conversion of chorismate to prephenate by computing the reaction energy profile in vacuo, aqueous solution and in the active site of the B. subtilis chorismate mutase enzyme. We have performed calculations for two different choices of the QM subsystem in the enzyme simulations: including only the substrate moiety and the substrate plus the charged side chains glu78 and arg90, respectively. In both cases, our results are in good agreement with experiment. The catalytic activity achieved by chorismate mutase relative to the uncatalyzed reaction in solution is due to both a minor destabilization of the substrate molecule by compression and a major electrostatic stabilization of the transition state, which reduce the activation energy of the reaction.
title A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
title_short A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
title_full A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
title_fullStr A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
title_full_unstemmed A DFT-based QM-MM approach designed for the treatment of large molecular systems: Application to chorismate mutase
title_sort dft-based qm-mm approach designed for the treatment of large molecular systems: application to chorismate mutase
publishDate 2003
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v107_n49_p13728_Crespo
http://hdl.handle.net/20.500.12110/paper_15206106_v107_n49_p13728_Crespo
_version_ 1768543100901261312

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