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 Biology
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.
(Less)
- author
- Caldararu, Octav
LU
; Manzoni, Francesco
LU
; Oksanen, Esko
LU
; Logan, Derek T.
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2019
- 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 Biology
- volume
- 75
- pages
- 13 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:30988254
- scopus:85064598747
- ISSN
- 2059-7983
- 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
- 2024-04-16 03:50:31
@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 = {{2059-7983}},
keywords = {{Galectin-3; Hydrogen atoms; Lytic polysaccharide monooxygenase; Neutron crystallography; Quantum chemistry; Quantum refinement; Refinement}},
language = {{eng}},
pages = {{368--380}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Acta Crystallographica Section D: Structural Biology}},
title = {{Refinement of protein structures using a combination of quantum-mechanical calculations with neutron and X-ray crystallographic data}},
url = {{https://lup.lub.lu.se/search/files/84187811/cqu_251.pdf}},
doi = {{10.1107/S205979831900175X}},
volume = {{75}},
year = {{2019}},
}