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Accurate reaction energies in proteins obtained by combining QM/MM and large QM calculations

Hu, LiHong LU ; Söderhjelm, Pär LU and Ryde, Ulf LU orcid (2013) In Journal of Chemical Theory and Computation 9. p.640-649
Abstract
We here suggest and test a new method to obtain stable energies in proteins for charge-neutral reactions by running large quantum mechanical (QM) calculations on structures obtained by combined QM and molecular mechanics (QM/MM) geometry optimisation on several snapshots from molecular dynamics simulations. As a test case, we use a proton transfer between a metal-bound cysteine residue and a second-sphere histidine residue in the active site of [Ni,Fe] hydrogenase, which has been shown to be very sensitive to the surroundings. We include in the QM calculations all residues within 4.5 Å of the active site, two capped residues on each side of the active-site residues, as well as all charged groups that are buried inside the protein, which... (More)
We here suggest and test a new method to obtain stable energies in proteins for charge-neutral reactions by running large quantum mechanical (QM) calculations on structures obtained by combined QM and molecular mechanics (QM/MM) geometry optimisation on several snapshots from molecular dynamics simulations. As a test case, we use a proton transfer between a metal-bound cysteine residue and a second-sphere histidine residue in the active site of [Ni,Fe] hydrogenase, which has been shown to be very sensitive to the surroundings. We include in the QM calculations all residues within 4.5 Å of the active site, two capped residues on each side of the active-site residues, as well as all charged groups that are buried inside the protein, which for this enzyme includes three iron–sulphur clusters, in total 930 atoms. These calculations are performed at the BP86/def2-SV(P) level, but the energies are then extrapolated to the B3LYP/def2-TZVP level with a smaller QM system and zero-point energy, entropy, and thermal effects are added. We test three approaches to model the remaining atoms of the protein solvent, viz. by standard QM/MM approaches using either mechanical or electrostatic embedding, or by using a continuum solvation model for the large QM systems. Quite encouragingly, the three approaches give the same results within 13 kJ/mol and variations in the size of the QM system do not change the energies by more than 8 kJ/mol, provided that the QM/MM junctions are not moved closer to the QM system. The statistical precision for the average over ten snapshots is 1–3 kJ/mol. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Quantum mechanical cluster calculations, QM/MM calculations, continuum solvation, large quantum mechanical calculations, proton transfer, [Ni, Fe] hydrogenase.
in
Journal of Chemical Theory and Computation
volume
9
pages
640 - 649
publisher
The American Chemical Society (ACS)
external identifiers
  • wos:000313378700064
  • scopus:84872130995
  • pmid:26589061
ISSN
1549-9618
DOI
10.1021/ct3005003
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
a4cc32bc-e8c1-4859-8beb-13dfd346901f (old id 3412412)
date added to LUP
2016-04-01 10:02:00
date last changed
2023-01-02 00:30:57
@article{a4cc32bc-e8c1-4859-8beb-13dfd346901f,
  abstract     = {{We here suggest and test a new method to obtain stable energies in proteins for charge-neutral reactions by running large quantum mechanical (QM) calculations on structures obtained by combined QM and molecular mechanics (QM/MM) geometry optimisation on several snapshots from molecular dynamics simulations. As a test case, we use a proton transfer between a metal-bound cysteine residue and a second-sphere histidine residue in the active site of [Ni,Fe] hydrogenase, which has been shown to be very sensitive to the surroundings. We include in the QM calculations all residues within 4.5 Å of the active site, two capped residues on each side of the active-site residues, as well as all charged groups that are buried inside the protein, which for this enzyme includes three iron–sulphur clusters, in total 930 atoms. These calculations are performed at the BP86/def2-SV(P) level, but the energies are then extrapolated to the B3LYP/def2-TZVP level with a smaller QM system and zero-point energy, entropy, and thermal effects are added. We test three approaches to model the remaining atoms of the protein solvent, viz. by standard QM/MM approaches using either mechanical or electrostatic embedding, or by using a continuum solvation model for the large QM systems. Quite encouragingly, the three approaches give the same results within 13 kJ/mol and variations in the size of the QM system do not change the energies by more than 8 kJ/mol, provided that the QM/MM junctions are not moved closer to the QM system. The statistical precision for the average over ten snapshots is 1–3 kJ/mol.}},
  author       = {{Hu, LiHong and Söderhjelm, Pär and Ryde, Ulf}},
  issn         = {{1549-9618}},
  keywords     = {{Quantum mechanical cluster calculations; QM/MM calculations; continuum solvation; large quantum mechanical calculations; proton transfer; [Ni; Fe] hydrogenase.}},
  language     = {{eng}},
  pages        = {{640--649}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Chemical Theory and Computation}},
  title        = {{Accurate reaction energies in proteins obtained by combining QM/MM and large QM calculations}},
  url          = {{https://lup.lub.lu.se/search/files/1496077/3412413.pdf}},
  doi          = {{10.1021/ct3005003}},
  volume       = {{9}},
  year         = {{2013}},
}