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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1243332
- author
- Söderhjelm, Pär
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Computational Chemistry
- volume
- 30
- issue
- 5
- pages
- 750 - 760
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000264225900007
- pmid:18773405
- scopus:64549135080
- pmid:18773405
- ISSN
- 1096-987X
- DOI
- 10.1002/jcc.21097
- 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
- 3d056f2b-0587-4cd8-a156-837948cc48d8 (old id 1243332)
- date added to LUP
- 2016-04-01 14:49:34
- date last changed
- 2023-02-07 02:35:28
@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 Inc.}},
series = {{Journal of Computational Chemistry}},
title = {{Conformational dependence of charges in protein simulations}},
url = {{https://lup.lub.lu.se/search/files/136745013/120_qm_charges.pdf}},
doi = {{10.1002/jcc.21097}},
volume = {{30}},
year = {{2009}},
}