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NMR structure determination of proteins supplemented by quantum chemical calculations: Detailed structure of the Ca2+ sites in the EGF34 fragment of protein S

Hsiao, Ya-Wen LU ; Drakenberg, Torbjörn LU and Ryde, Ulf LU (2005) In Journal of Biomolecular NMR 31(2). p.97-114
Abstract
We present and test two methods to use quantum chemical calculations to improve standard protein structure refinement by molecular dynamics simulations restrained to experimental NMR data. In the first, we replace the molecular mechanics force field ( employed in standard refinement to supplement experimental data) for a site of interest by quantum chemical calculations. This way, we obtain an accurate description of the site, even if a molecular mechanics force field does not exist for this site, or if there is little experimental information about the site. Moreover, the site may change its bonding during the refinement, which often is the case for metal sites. The second method is to extract a molecular mechanics potential for the site... (More)
We present and test two methods to use quantum chemical calculations to improve standard protein structure refinement by molecular dynamics simulations restrained to experimental NMR data. In the first, we replace the molecular mechanics force field ( employed in standard refinement to supplement experimental data) for a site of interest by quantum chemical calculations. This way, we obtain an accurate description of the site, even if a molecular mechanics force field does not exist for this site, or if there is little experimental information about the site. Moreover, the site may change its bonding during the refinement, which often is the case for metal sites. The second method is to extract a molecular mechanics potential for the site of interest from a quantum chemical geometry optimisation and frequency calculation. We apply both methods to the two Ca2+ sites in the epidermal growth factor-like domains 3 and 4 in the vitamin K-dependent protein S and compare them to various methods to treat these sites in standard refinement. We show that both methods perform well and have their advantages and disadvantages. We also show that the glutamate Ca2+ ligand is unlikely to bind in a bidentate mode, in contrast to the crystal structure of an EGF domain of factor IX. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biomolecular NMR
volume
31
issue
2
pages
97 - 114
publisher
Springer
external identifiers
  • wos:000227735100002
  • pmid:15772750
  • scopus:15844393284
ISSN
1573-5001
DOI
10.1007/s10858-004-6729-7
language
English
LU publication?
yes
id
7a5f7c0f-1079-4507-a08d-643c9bb8275b (old id 151544)
date added to LUP
2007-06-29 11:14:49
date last changed
2017-01-01 04:41:45
@article{7a5f7c0f-1079-4507-a08d-643c9bb8275b,
  abstract     = {We present and test two methods to use quantum chemical calculations to improve standard protein structure refinement by molecular dynamics simulations restrained to experimental NMR data. In the first, we replace the molecular mechanics force field ( employed in standard refinement to supplement experimental data) for a site of interest by quantum chemical calculations. This way, we obtain an accurate description of the site, even if a molecular mechanics force field does not exist for this site, or if there is little experimental information about the site. Moreover, the site may change its bonding during the refinement, which often is the case for metal sites. The second method is to extract a molecular mechanics potential for the site of interest from a quantum chemical geometry optimisation and frequency calculation. We apply both methods to the two Ca2+ sites in the epidermal growth factor-like domains 3 and 4 in the vitamin K-dependent protein S and compare them to various methods to treat these sites in standard refinement. We show that both methods perform well and have their advantages and disadvantages. We also show that the glutamate Ca2+ ligand is unlikely to bind in a bidentate mode, in contrast to the crystal structure of an EGF domain of factor IX.},
  author       = {Hsiao, Ya-Wen and Drakenberg, Torbjörn and Ryde, Ulf},
  issn         = {1573-5001},
  language     = {eng},
  number       = {2},
  pages        = {97--114},
  publisher    = {Springer},
  series       = {Journal of Biomolecular NMR},
  title        = {NMR structure determination of proteins supplemented by quantum chemical calculations: Detailed structure of the Ca2+ sites in the EGF34 fragment of protein S},
  url          = {http://dx.doi.org/10.1007/s10858-004-6729-7},
  volume       = {31},
  year         = {2005},
}