QM/MM-PBSA method to estimate free energies for reactions in proteins
Kaukonen, Markus LU ; Söderhjelm, Pär LU ; Heimdal, Jimmy LU and Ryde, Ulf LU
(2008)
In The Journal of Physical Chemistry Part B
112(39).
p.12537-12548
- Abstract
- We have developed a method to estimate free energies of reactions in proteins, called QM/MM-PBSA. It estimates the internal energy of the reactive site by quantum mechanical (QM) calculations, whereas bonded, electrostatic, and van der Waals interactions with the surrounding protein are calculated at the molecular mechanics (MM) level. The electrostatic part of the solvation energy of the reactant and the product is estimated by solving the Poisson-Boltzmann (PB) equation, and the nonpolar part of the solvation energy is estimated from the change in solvent-accessible surface area (SA). Finally, the change in entropy is estimated from the vibrational frequencies. We test this method for five proton-transfer reactions in the active sites of... (More)
- We have developed a method to estimate free energies of reactions in proteins, called QM/MM-PBSA. It estimates the internal energy of the reactive site by quantum mechanical (QM) calculations, whereas bonded, electrostatic, and van der Waals interactions with the surrounding protein are calculated at the molecular mechanics (MM) level. The electrostatic part of the solvation energy of the reactant and the product is estimated by solving the Poisson-Boltzmann (PB) equation, and the nonpolar part of the solvation energy is estimated from the change in solvent-accessible surface area (SA). Finally, the change in entropy is estimated from the vibrational frequencies. We test this method for five proton-transfer reactions in the active sites of [Ni,Fe] hydrogenase and copper nitrite. reductase. We show that QM/MM-PBSA reproduces the results of a strict QM/MM free-energy perturbation method with a mean absolute deviation (MAD) of 8-10 kJ/mol if snapshots from molecular dynamics simulations are used and 4-14 kJ/mol if a single QM/MM structure is used. This is appreciably better than the original QM/MM results or if the QM energies are supplemented with a point-charge model, a self-consistent reaction field, or a PB model of the protein and the solvent, which give MADs of 22-36 kJ/mol for the same test set. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1286622
- author
- Kaukonen, Markus
LU
; Söderhjelm, Pär
LU
; Heimdal, Jimmy
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Physical Chemistry Part B
- volume
- 112
- issue
- 39
- pages
- 12537 - 12548
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000259552000047
- scopus:54249114557
- pmid:18781715
- ISSN
- 1520-5207
- DOI
- 10.1021/jp802648k
- 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
- 9221316c-295c-4b13-8bdc-cdf8898526f7 (old id 1286622)
- date added to LUP
- 2016-04-01 13:22:09
- date last changed
- 2023-04-06 05:04:31
@article{9221316c-295c-4b13-8bdc-cdf8898526f7,
abstract = {{We have developed a method to estimate free energies of reactions in proteins, called QM/MM-PBSA. It estimates the internal energy of the reactive site by quantum mechanical (QM) calculations, whereas bonded, electrostatic, and van der Waals interactions with the surrounding protein are calculated at the molecular mechanics (MM) level. The electrostatic part of the solvation energy of the reactant and the product is estimated by solving the Poisson-Boltzmann (PB) equation, and the nonpolar part of the solvation energy is estimated from the change in solvent-accessible surface area (SA). Finally, the change in entropy is estimated from the vibrational frequencies. We test this method for five proton-transfer reactions in the active sites of [Ni,Fe] hydrogenase and copper nitrite. reductase. We show that QM/MM-PBSA reproduces the results of a strict QM/MM free-energy perturbation method with a mean absolute deviation (MAD) of 8-10 kJ/mol if snapshots from molecular dynamics simulations are used and 4-14 kJ/mol if a single QM/MM structure is used. This is appreciably better than the original QM/MM results or if the QM energies are supplemented with a point-charge model, a self-consistent reaction field, or a PB model of the protein and the solvent, which give MADs of 22-36 kJ/mol for the same test set.}},
author = {{Kaukonen, Markus and Söderhjelm, Pär and Heimdal, Jimmy and Ryde, Ulf}},
issn = {{1520-5207}},
language = {{eng}},
number = {{39}},
pages = {{12537--12548}},
publisher = {{The American Chemical Society (ACS)}},
series = {{The Journal of Physical Chemistry Part B}},
title = {{QM/MM-PBSA method to estimate free energies for reactions in proteins}},
url = {{https://lup.lub.lu.se/search/files/136745504/114_qmmm_pbsa.pdf}},
doi = {{10.1021/jp802648k}},
volume = {{112}},
year = {{2008}},
}