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Quantum mechanical free energy barrier for an enzymatic reaction

Rod, Thomas LU and Ryde, Ulf LU (2005) In Physical Review Letters 94(13). p.1-138302
Abstract
We discuss problems related to in silico studies of enzymes and show that accurate and converged free energy changes for complex chemical reactions can be computed if a method based on a thermodynamic cycle is employed. The method combines the sampling speed of molecular mechanics with the accuracy of a high-level quantum mechanics method. We use the method to compute the free energy barrier for a methyl transfer reaction catalyzed by the enzyme catechol O-methyltransferase at the level of density functional theory. The surrounding protein and solvent are found to have a profound effect on the reaction, and we show that energies can be extrapolated easily from one basis set and exchange-correlation functional to another. Using this... (More)
We discuss problems related to in silico studies of enzymes and show that accurate and converged free energy changes for complex chemical reactions can be computed if a method based on a thermodynamic cycle is employed. The method combines the sampling speed of molecular mechanics with the accuracy of a high-level quantum mechanics method. We use the method to compute the free energy barrier for a methyl transfer reaction catalyzed by the enzyme catechol O-methyltransferase at the level of density functional theory. The surrounding protein and solvent are found to have a profound effect on the reaction, and we show that energies can be extrapolated easily from one basis set and exchange-correlation functional to another. Using this procedure we calculate a barrier of 69 kJ/mol, in excellent agreement with the experimental value of 75 kJ/mol. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physical Review Letters
volume
94
issue
13
pages
1 - 138302
publisher
American Physical Society
external identifiers
  • wos:000228289000073
  • scopus:18144410229
ISSN
1079-7114
DOI
10.1103/PhysRevLett.94.138302
language
English
LU publication?
yes
id
2e14cb37-281a-4b0d-b48c-b3e269a125d4 (old id 152759)
date added to LUP
2007-07-17 13:22:11
date last changed
2017-09-24 03:46:35
@article{2e14cb37-281a-4b0d-b48c-b3e269a125d4,
  abstract     = {We discuss problems related to in silico studies of enzymes and show that accurate and converged free energy changes for complex chemical reactions can be computed if a method based on a thermodynamic cycle is employed. The method combines the sampling speed of molecular mechanics with the accuracy of a high-level quantum mechanics method. We use the method to compute the free energy barrier for a methyl transfer reaction catalyzed by the enzyme catechol O-methyltransferase at the level of density functional theory. The surrounding protein and solvent are found to have a profound effect on the reaction, and we show that energies can be extrapolated easily from one basis set and exchange-correlation functional to another. Using this procedure we calculate a barrier of 69 kJ/mol, in excellent agreement with the experimental value of 75 kJ/mol.},
  author       = {Rod, Thomas and Ryde, Ulf},
  issn         = {1079-7114},
  language     = {eng},
  number       = {13},
  pages        = {1--138302},
  publisher    = {American Physical Society},
  series       = {Physical Review Letters},
  title        = {Quantum mechanical free energy barrier for an enzymatic reaction},
  url          = {http://dx.doi.org/10.1103/PhysRevLett.94.138302},
  volume       = {94},
  year         = {2005},
}