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:
https://lup.lub.lu.se/record/152759
- author
- Rod, Thomas
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2005
- 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:85051912728
- ISSN
- 1079-7114
- DOI
- 10.1103/PhysRevLett.94.138302
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- 2e14cb37-281a-4b0d-b48c-b3e269a125d4 (old id 152759)
- date added to LUP
- 2016-04-01 12:30:58
- date last changed
- 2023-01-24 02:30:38
@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 = {{https://lup.lub.lu.se/search/files/135493059/75_qtcp1.pdf}},
doi = {{10.1103/PhysRevLett.94.138302}},
volume = {{94}},
year = {{2005}},
}