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Conformational dependence of charges in protein simulations.

Söderhjelm, Pär LU and Ryde, Ulf LU (2009) In Journal of Computational Chemistry 30(5). p.750-760
Abstract
We have studied the conformational dependence of molecular mechanics atomic charges for proteins by calculating the charges fitted to the quantum mechanical (QM) electrostatic potential (ESP) for all atoms in complexes between avidin and seven biotin analogues for 20 snapshots from molecular dynamics simulations. We have studied how various other charge sets reproduce those charges. The QM charges, even if averaged over all snapshots or all residues, in general have a larger magnitude than standard Amber charges, indicating that the restraint toward zero in the restrained ESP method is too strong. This has a significant influence on the electrostatic conformational energies and the interaction energy between the biotin ligand and the... (More)
We have studied the conformational dependence of molecular mechanics atomic charges for proteins by calculating the charges fitted to the quantum mechanical (QM) electrostatic potential (ESP) for all atoms in complexes between avidin and seven biotin analogues for 20 snapshots from molecular dynamics simulations. We have studied how various other charge sets reproduce those charges. The QM charges, even if averaged over all snapshots or all residues, in general have a larger magnitude than standard Amber charges, indicating that the restraint toward zero in the restrained ESP method is too strong. This has a significant influence on the electrostatic conformational energies and the interaction energy between the biotin ligand and the protein, giving a difference between the QM and Amber charges of 43 and 8 kJ/mol for the negatively charged and neutral biotin analogues, respectively (3-4%). However, this energy difference is strongly reduced if the solvation energy (calculated by the Poisson-Boltzmann or Generalized Born methods) is added, viz., to 7 kJ/mol for charged and 3 kJ/mol for uncharged ligand. In fact, charges need to be recalculated with a QM method only for residues within 7 or 4 A of the ligand, if the error should be less than 4 kJ/mol. Unfortunately, the QM charges do not give significantly better MM/PBSA estimates of ligand-binding affinities than standard Amber charges. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Computational Chemistry
volume
30
issue
5
pages
750 - 760
publisher
John Wiley & Sons
external identifiers
  • wos:000264225900007
  • pmid:18773405
  • scopus:64549135080
ISSN
1096-987X
DOI
10.1002/jcc.21097
language
English
LU publication?
yes
id
3d056f2b-0587-4cd8-a156-837948cc48d8 (old id 1243332)
date added to LUP
2009-03-16 10:51:57
date last changed
2017-09-10 04:19:24
@article{3d056f2b-0587-4cd8-a156-837948cc48d8,
  abstract     = {We have studied the conformational dependence of molecular mechanics atomic charges for proteins by calculating the charges fitted to the quantum mechanical (QM) electrostatic potential (ESP) for all atoms in complexes between avidin and seven biotin analogues for 20 snapshots from molecular dynamics simulations. We have studied how various other charge sets reproduce those charges. The QM charges, even if averaged over all snapshots or all residues, in general have a larger magnitude than standard Amber charges, indicating that the restraint toward zero in the restrained ESP method is too strong. This has a significant influence on the electrostatic conformational energies and the interaction energy between the biotin ligand and the protein, giving a difference between the QM and Amber charges of 43 and 8 kJ/mol for the negatively charged and neutral biotin analogues, respectively (3-4%). However, this energy difference is strongly reduced if the solvation energy (calculated by the Poisson-Boltzmann or Generalized Born methods) is added, viz., to 7 kJ/mol for charged and 3 kJ/mol for uncharged ligand. In fact, charges need to be recalculated with a QM method only for residues within 7 or 4 A of the ligand, if the error should be less than 4 kJ/mol. Unfortunately, the QM charges do not give significantly better MM/PBSA estimates of ligand-binding affinities than standard Amber charges. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.},
  author       = {Söderhjelm, Pär and Ryde, Ulf},
  issn         = {1096-987X},
  language     = {eng},
  number       = {5},
  pages        = {750--760},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Computational Chemistry},
  title        = {Conformational dependence of charges in protein simulations.},
  url          = {http://dx.doi.org/10.1002/jcc.21097},
  volume       = {30},
  year         = {2009},
}