Protonation status of metal-bound ligands can be determined by quantum refinement
Nilsson, Kristina LU and Ryde, Ulf LU
(2004)
In Journal of Inorganic Biochemistry
98(9).
p.1539-1546
- Abstract
- The protonation status of key residues and bound ligands are often important for the function of a protein. Unfortunately, protons are not discerned in normal protein crystal structures, so their positions have to be determined by more indirect methods. We show that the recently developed quantum refinement method can be used to determine the position of protons in crystal structures. By replacing the molecular-mechanics potential, normally used in crystallographic refinement, by more accurate quantum chemical calculations, we get information about the ideal structure of a certain protonation state. By comparing the refined structures of different protonation states, the one that fits the crystallographic raw data best can be decided using... (More)
- The protonation status of key residues and bound ligands are often important for the function of a protein. Unfortunately, protons are not discerned in normal protein crystal structures, so their positions have to be determined by more indirect methods. We show that the recently developed quantum refinement method can be used to determine the position of protons in crystal structures. By replacing the molecular-mechanics potential, normally used in crystallographic refinement, by more accurate quantum chemical calculations, we get information about the ideal structure of a certain protonation state. By comparing the refined structures of different protonation states, the one that fits the crystallographic raw data best can be decided using four criteria: the R factors, electron density maps, strain energy, and divergence from the unrestrained quantum chemical structure. We test this method on alcohol dehydrogenase, for which the pK(a) of the zinc-bound solvent molecule is experimentally known. We show that we can predict the correct protonation state for both a deprotonated alcohol and a neutral water molecule. (C) 2004 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/139601
- author
- Nilsson, Kristina
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Inorganic Biochemistry
- volume
- 98
- issue
- 9
- pages
- 1539 - 1546
- publisher
- Elsevier
- external identifiers
-
- wos:000224010300008
- pmid:15337606
- scopus:4444253515
- ISSN
- 1873-3344
- DOI
- 10.1016/j.jinorgbio.2004.06.006
- 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
- 9a549533-a6ea-4de8-8624-0e3c0a8e1afa (old id 139601)
- date added to LUP
- 2016-04-01 16:22:34
- date last changed
- 2023-01-24 02:30:35
@article{9a549533-a6ea-4de8-8624-0e3c0a8e1afa,
abstract = {{The protonation status of key residues and bound ligands are often important for the function of a protein. Unfortunately, protons are not discerned in normal protein crystal structures, so their positions have to be determined by more indirect methods. We show that the recently developed quantum refinement method can be used to determine the position of protons in crystal structures. By replacing the molecular-mechanics potential, normally used in crystallographic refinement, by more accurate quantum chemical calculations, we get information about the ideal structure of a certain protonation state. By comparing the refined structures of different protonation states, the one that fits the crystallographic raw data best can be decided using four criteria: the R factors, electron density maps, strain energy, and divergence from the unrestrained quantum chemical structure. We test this method on alcohol dehydrogenase, for which the pK(a) of the zinc-bound solvent molecule is experimentally known. We show that we can predict the correct protonation state for both a deprotonated alcohol and a neutral water molecule. (C) 2004 Elsevier Inc. All rights reserved.}},
author = {{Nilsson, Kristina and Ryde, Ulf}},
issn = {{1873-3344}},
language = {{eng}},
number = {{9}},
pages = {{1539--1546}},
publisher = {{Elsevier}},
series = {{Journal of Inorganic Biochemistry}},
title = {{Protonation status of metal-bound ligands can be determined by quantum refinement}},
url = {{https://lup.lub.lu.se/search/files/135492592/67_prot.pdf}},
doi = {{10.1016/j.jinorgbio.2004.06.006}},
volume = {{98}},
year = {{2004}},
}