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Implicit versus explicit solvent in free energy calculations of enzyme catalysis: Methyl transfer catalyzed by catechol O-methyltransferase

Rod, Thomas LU ; Rydberg, Patrik LU and Ryde, Ulf LU orcid (2006) In Journal of Chemical Physics 124(17).
Abstract
We compare free energy calculations for the methyl transfer reaction catalyzed by catechol O-methyltransferase using the quantum mechanical/molecular mechanical free energy method with implicit and explicit solvents. An analogous methylation reaction in a solution is also studied. For the explicit solvent model, we use the three-point transferable intermolecular potential model, and for the implicit model, we use the generalized Born molecular volume model as implemented in CHARMM. We find that activation and reaction free energies calculated with the two models are very similar, despite some structural differences that exist. A significant change in the polarization of the environment occurs as the reaction proceeds. This is more... (More)
We compare free energy calculations for the methyl transfer reaction catalyzed by catechol O-methyltransferase using the quantum mechanical/molecular mechanical free energy method with implicit and explicit solvents. An analogous methylation reaction in a solution is also studied. For the explicit solvent model, we use the three-point transferable intermolecular potential model, and for the implicit model, we use the generalized Born molecular volume model as implemented in CHARMM. We find that activation and reaction free energies calculated with the two models are very similar, despite some structural differences that exist. A significant change in the polarization of the environment occurs as the reaction proceeds. This is more pronounced for the reaction in a solution than for the enzymatic reaction. For the enzymatic reaction, most of the changes take place in the protein rather than in the solvent, and, hence, the benefit of having an instantaneous relaxation of the solvent degrees of freedom is less pronounced for the enzymatic reaction than for the reaction in a solution. This is a likely reason why energies of the enzyme reaction are less sensitive to the choice of atomic radii than are energies of the reaction in a solution. (c) 2006 American Institute of Physics. (Less)
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publication status
published
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in
Journal of Chemical Physics
volume
124
issue
17
article number
174503
publisher
American Institute of Physics (AIP)
external identifiers
  • wos:000237321700021
  • scopus:34547926027
  • pmid:16689579
ISSN
0021-9606
DOI
10.1063/1.2186635
language
English
LU publication?
yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Theoretical Chemistry (S) (011001039)
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0dcc955c-62a0-42d4-9634-bd3ca9b274cd (old id 410072)
date added to LUP
2016-04-01 12:20:52
date last changed
2021-09-01 04:20:26
@article{0dcc955c-62a0-42d4-9634-bd3ca9b274cd,
  abstract     = {We compare free energy calculations for the methyl transfer reaction catalyzed by catechol O-methyltransferase using the quantum mechanical/molecular mechanical free energy method with implicit and explicit solvents. An analogous methylation reaction in a solution is also studied. For the explicit solvent model, we use the three-point transferable intermolecular potential model, and for the implicit model, we use the generalized Born molecular volume model as implemented in CHARMM. We find that activation and reaction free energies calculated with the two models are very similar, despite some structural differences that exist. A significant change in the polarization of the environment occurs as the reaction proceeds. This is more pronounced for the reaction in a solution than for the enzymatic reaction. For the enzymatic reaction, most of the changes take place in the protein rather than in the solvent, and, hence, the benefit of having an instantaneous relaxation of the solvent degrees of freedom is less pronounced for the enzymatic reaction than for the reaction in a solution. This is a likely reason why energies of the enzyme reaction are less sensitive to the choice of atomic radii than are energies of the reaction in a solution. (c) 2006 American Institute of Physics.},
  author       = {Rod, Thomas and Rydberg, Patrik and Ryde, Ulf},
  issn         = {0021-9606},
  language     = {eng},
  number       = {17},
  publisher    = {American Institute of Physics (AIP)},
  series       = {Journal of Chemical Physics},
  title        = {Implicit versus explicit solvent in free energy calculations of enzyme catalysis: Methyl transfer catalyzed by catechol O-methyltransferase},
  url          = {http://dx.doi.org/10.1063/1.2186635},
  doi          = {10.1063/1.2186635},
  volume       = {124},
  year         = {2006},
}