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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)
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author
organization
publishing date
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
external identifiers
  • wos:000259552000047
  • scopus:54249114557
ISSN
1520-5207
DOI
10.1021/jp802648k
language
English
LU publication?
yes
id
9221316c-295c-4b13-8bdc-cdf8898526f7 (old id 1286622)
date added to LUP
2009-02-04 08:47:34
date last changed
2017-09-24 03:55:31
@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},
  series       = {The Journal of Physical Chemistry Part B},
  title        = {QM/MM-PBSA method to estimate free energies for reactions in proteins},
  url          = {http://dx.doi.org/10.1021/jp802648k},
  volume       = {112},
  year         = {2008},
}