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Refinement of protein structures using a combination of quantum-mechanical calculations with neutron and X-ray crystallographic data

Caldararu, Octav LU ; Manzoni, Francesco LU ; Oksanen, Esko LU ; Logan, Derek T. LU and Ryde, Ulf LU (2019) In Acta Crystallographica Section D: Structural Biology2016-01-01+01:00 75. p.368-380
Abstract

Neutron crystallography is a powerful method to determine the positions of H atoms in macromolecular structures. However, it is sometimes hard to judge what would constitute a chemically reasonable model, and the geometry of H atoms depends more on the surroundings (for example the formation of hydrogen bonds) than heavy atoms, so that the empirical geometry information for the H atoms used to supplement the experimental data is often less accurate. These problems may be reduced by using quantum-mechanical calculations. A method has therefore been developed to combine quantum-mechanical calculations with joint crystallographic refinement against X-ray and neutron data. A first validation of this method is provided by re-refining the... (More)

Neutron crystallography is a powerful method to determine the positions of H atoms in macromolecular structures. However, it is sometimes hard to judge what would constitute a chemically reasonable model, and the geometry of H atoms depends more on the surroundings (for example the formation of hydrogen bonds) than heavy atoms, so that the empirical geometry information for the H atoms used to supplement the experimental data is often less accurate. These problems may be reduced by using quantum-mechanical calculations. A method has therefore been developed to combine quantum-mechanical calculations with joint crystallographic refinement against X-ray and neutron data. A first validation of this method is provided by re-refining the structure of the galectin-3 carbohydrate-recognition domain in complex with lactose. The geometry is improved, in particular for water molecules, for which the method leads to better-resolved hydrogen-bonding interactions. The method has also been applied to the active copper site of lytic polysaccharide monooxygenase and shows that the protonation state of the amino-terminal histidine residue can be determined.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Galectin-3, Hydrogen atoms, Lytic polysaccharide monooxygenase, Neutron crystallography, Quantum chemistry, Quantum refinement, Refinement
in
Acta Crystallographica Section D: Structural Biology2016-01-01+01:00
volume
75
pages
13 pages
publisher
John Wiley and Sons Inc.
external identifiers
  • scopus:85064598747
ISSN
0907-4449
DOI
10.1107/S205979831900175X
language
English
LU publication?
yes
id
d8875ecd-36c0-4bca-bb56-35cc78f5fc3a
date added to LUP
2019-05-03 12:53:01
date last changed
2019-08-04 05:28:05
@article{d8875ecd-36c0-4bca-bb56-35cc78f5fc3a,
  abstract     = {<p>Neutron crystallography is a powerful method to determine the positions of H atoms in macromolecular structures. However, it is sometimes hard to judge what would constitute a chemically reasonable model, and the geometry of H atoms depends more on the surroundings (for example the formation of hydrogen bonds) than heavy atoms, so that the empirical geometry information for the H atoms used to supplement the experimental data is often less accurate. These problems may be reduced by using quantum-mechanical calculations. A method has therefore been developed to combine quantum-mechanical calculations with joint crystallographic refinement against X-ray and neutron data. A first validation of this method is provided by re-refining the structure of the galectin-3 carbohydrate-recognition domain in complex with lactose. The geometry is improved, in particular for water molecules, for which the method leads to better-resolved hydrogen-bonding interactions. The method has also been applied to the active copper site of lytic polysaccharide monooxygenase and shows that the protonation state of the amino-terminal histidine residue can be determined.</p>},
  author       = {Caldararu, Octav and Manzoni, Francesco and Oksanen, Esko and Logan, Derek T. and Ryde, Ulf},
  issn         = {0907-4449},
  keyword      = {Galectin-3,Hydrogen atoms,Lytic polysaccharide monooxygenase,Neutron crystallography,Quantum chemistry,Quantum refinement,Refinement},
  language     = {eng},
  pages        = {368--380},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Acta Crystallographica Section D: Structural Biology2016-01-01+01:00},
  title        = {Refinement of protein structures using a combination of quantum-mechanical calculations with neutron and X-ray crystallographic data},
  url          = {http://dx.doi.org/10.1107/S205979831900175X},
  volume       = {75},
  year         = {2019},
}