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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)
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author
organization
publishing date
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
id
9a549533-a6ea-4de8-8624-0e3c0a8e1afa (old id 139601)
date added to LUP
2007-07-17 12:09:13
date last changed
2017-09-24 04:26:24
@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          = {http://dx.doi.org/10.1016/j.jinorgbio.2004.06.006},
  volume       = {98},
  year         = {2004},
}