Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Quantum refinement with electron diffraction and X-ray free-electron laser data: comparative study of ribonucleotide reductase dimetal site

Lundgren, Kristoffer J. M. LU ; Sun, Xiaoli LU ; Pacoste, Laura ; Kumar, Rohit LU ; Hofer, Gerhard ; Xu, Hongyi ; Zou, Xiaodong ; Högbom, Martin ; Oksanen, Esko LU and Ryde, Ulf LU orcid (2026) In Journal of Applied Crystallography 59(2). p.277-290
Abstract
Quantum refinement (QR) is an approach in which the empirical restraints used in standard structural refinement to ensure that the details of the structure, e.g.
bond lengths and angles, make chemical sense are replaced by more
accurate quantum mechanical calculations for a small but interesting
part of the structure. QR has previously been used for X-ray and neutron
crystallography, cryogenic electron microscopy,
nuclear magnetic resonance, and extended X-ray absorption fine
structure. Here, QR is used for the first time for X-ray free-electron
laser (XFEL) crystallography and microcrystal electron diffraction
(MicroED). As a test case, we use six structures of the R2a protein of
... (More)
Quantum refinement (QR) is an approach in which the empirical restraints used in standard structural refinement to ensure that the details of the structure, e.g.
bond lengths and angles, make chemical sense are replaced by more
accurate quantum mechanical calculations for a small but interesting
part of the structure. QR has previously been used for X-ray and neutron
crystallography, cryogenic electron microscopy,
nuclear magnetic resonance, and extended X-ray absorption fine
structure. Here, QR is used for the first time for X-ray free-electron
laser (XFEL) crystallography and microcrystal electron diffraction
(MicroED). As a test case, we use six structures of the R2a protein of
ribonucleotide reductase, concentrating on the binuclear Fe2 site in either the oxidized (Fe2III) or reduced (Fe2II)
state, two each from single-crystal X-ray (SCX) crystallography, XFEL
crystallography or MicroED. The results show that QR works well for data
from all three radiation sources, even though scattering factors for
neutral atoms had to be used for MicroED. QR corrects unrealistically
short Fe—O distances in the reduced SCX structure and gives improved
real-space Z scores for the reduced
MicroED structure. The three methods give similar structures, apart from
variation in the weak water ligands and in the binding of carboxylate
groups (monodentate, bidentate or a mixture). By performing QR for three
protonation states of the bridging solvent molecule, we could show that
it is undoubtedly a water molecule in the reduced XFEL and MicroED
structures (it is not present in the SCX structure) and that it is not
water in the oxidized structures. The XFEL data indicate that it is O2− in the oxidized XFEL structure, in agreement with the spectroscopic results. However, for the SCX structure, O2− and OH− give comparable results, whereas OH−
is slightly preferred in the MicroED structure. This indicates that the
SCX and MicroED structures may be partly photoreduced during data
collection. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Applied Crystallography
volume
59
issue
2
pages
14 pages
publisher
International Union of Crystallography
external identifiers
  • pmid:41959874
  • scopus:105037418610
ISSN
1600-5767
DOI
10.1107/S1600576725011264
language
English
LU publication?
yes
id
fa6770bf-9ba9-4396-bbd2-bdcd832ac6f9
date added to LUP
2026-04-03 10:10:04
date last changed
2026-07-16 04:00:43
@article{fa6770bf-9ba9-4396-bbd2-bdcd832ac6f9,
  abstract     = {{Quantum refinement (QR) is an approach in which the empirical restraints used in standard structural refinement to ensure that the details of the structure, <i>e.g.</i><br>
 bond lengths and angles, make chemical sense are replaced by more <br>
accurate quantum mechanical calculations for a small but interesting <br>
part of the structure. QR has previously been used for X-ray and neutron<br>
 crystallography, cryogenic electron microscopy,<br>
 nuclear magnetic resonance, and extended X-ray absorption fine <br>
structure. Here, QR is used for the first time for X-ray free-electron <br>
laser (XFEL) crystallography and microcrystal electron diffraction <br>
(MicroED). As a test case, we use six structures of the R2a protein of <br>
ribonucleotide reductase, concentrating on the binuclear Fe<sub>2</sub> site in either the oxidized (Fe<sub>2</sub><sup>III</sup>) or reduced (Fe<sub>2</sub><sup>II</sup>)<br>
 state, two each from single-crystal X-ray (SCX) crystallography, XFEL <br>
crystallography or MicroED. The results show that QR works well for data<br>
 from all three radiation sources, even though scattering factors for <br>
neutral atoms had to be used for MicroED. QR corrects unrealistically <br>
short Fe—O distances in the reduced SCX structure and gives improved <br>
real-space <i>Z</i> scores for the reduced <br>
MicroED structure. The three methods give similar structures, apart from<br>
 variation in the weak water ligands and in the binding of carboxylate <br>
groups (monodentate, bidentate or a mixture). By performing QR for three<br>
 protonation states of the bridging solvent molecule, we could show that<br>
 it is undoubtedly a water molecule in the reduced XFEL and MicroED <br>
structures (it is not present in the SCX structure) and that it is not <br>
water in the oxidized structures. The XFEL data indicate that it is O<sup>2−</sup> in the oxidized XFEL structure, in agreement with the spectroscopic results. However, for the SCX structure, O<sup>2−</sup> and OH<sup>−</sup> give comparable results, whereas OH<sup>−</sup><br>
 is slightly preferred in the MicroED structure. This indicates that the<br>
 SCX and MicroED structures may be partly photoreduced during data <br>
collection.}},
  author       = {{Lundgren, Kristoffer J. M. and Sun, Xiaoli and Pacoste, Laura and Kumar, Rohit and Hofer, Gerhard and Xu, Hongyi and Zou, Xiaodong and Högbom, Martin and Oksanen, Esko and Ryde, Ulf}},
  issn         = {{1600-5767}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{2}},
  pages        = {{277--290}},
  publisher    = {{International Union of Crystallography}},
  series       = {{Journal of Applied Crystallography}},
  title        = {{Quantum refinement with electron diffraction and X-ray free-electron laser data: comparative study of ribonucleotide reductase dimetal site}},
  url          = {{http://dx.doi.org/10.1107/S1600576725011264}},
  doi          = {{10.1107/S1600576725011264}},
  volume       = {{59}},
  year         = {{2026}},
}