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Do quantum mechanical energies calculated for small models of protein-active sites converge?

Hu, LiHong LU ; Eliasson, Jenny; Heimdal, Jimmy LU and Ryde, Ulf LU (2009) In Journal of physical chemistry. A 113(43). p.11793-11800
Abstract
A common approach for the computational modeling of enzyme reactions is to study a rather small model of the active site (20-200 atoms) with quantum mechanical (QM) methods, modeling the rest of the surroundings by a featureless continuum with a dielectric constant of approximately 4. In this paper, we discuss how the residues included in the QM model should be selected and how many residues need to be included before reaction energies converge. As a test case, we use a proton-transfer reaction between a first-sphere cysteine ligand and a second-sphere histidine group in the active site of [Ni,Fe] hydrogenase. We show that it is not a good approach to add groups according to their distance to the active site. A better approach is to add... (More)
A common approach for the computational modeling of enzyme reactions is to study a rather small model of the active site (20-200 atoms) with quantum mechanical (QM) methods, modeling the rest of the surroundings by a featureless continuum with a dielectric constant of approximately 4. In this paper, we discuss how the residues included in the QM model should be selected and how many residues need to be included before reaction energies converge. As a test case, we use a proton-transfer reaction between a first-sphere cysteine ligand and a second-sphere histidine group in the active site of [Ni,Fe] hydrogenase. We show that it is not a good approach to add groups according to their distance to the active site. A better approach is to add groups according to their contributions to the QM/MM energy difference. However, the energies can still vary by up to 50 kJ/mol for QM systems of sizes up to 230 atoms. In fact, the QM-only approach is based on the hope that a large number of sizable contributions will cancel. Interactions with neutral groups are, in general, short-ranged, with net energy contributions of less than 4 kJ/mol at distances above 5 A from the active site. Interactions with charged groups are much more long-ranged, and interactions with buried charges 20 A from the active site can still contribute by 5 kJ/mol to the reaction energy. Thus, to accurately model the influence of the surroundings on enzyme reaction energies, a detailed and unbiased atomistic account of the surroundings needs to be included. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of physical chemistry. A
volume
113
issue
43
pages
11793 - 11800
publisher
The American Chemical Society
external identifiers
  • wos:000270911400040
  • pmid:19785474
  • scopus:70350432531
ISSN
1520-5215
DOI
10.1021/jp9029024
language
English
LU publication?
yes
id
c2521771-84be-440b-a561-0b0a18ff29ce (old id 1500947)
date added to LUP
2009-12-01 10:22:51
date last changed
2017-09-24 03:50:32
@article{c2521771-84be-440b-a561-0b0a18ff29ce,
  abstract     = {A common approach for the computational modeling of enzyme reactions is to study a rather small model of the active site (20-200 atoms) with quantum mechanical (QM) methods, modeling the rest of the surroundings by a featureless continuum with a dielectric constant of approximately 4. In this paper, we discuss how the residues included in the QM model should be selected and how many residues need to be included before reaction energies converge. As a test case, we use a proton-transfer reaction between a first-sphere cysteine ligand and a second-sphere histidine group in the active site of [Ni,Fe] hydrogenase. We show that it is not a good approach to add groups according to their distance to the active site. A better approach is to add groups according to their contributions to the QM/MM energy difference. However, the energies can still vary by up to 50 kJ/mol for QM systems of sizes up to 230 atoms. In fact, the QM-only approach is based on the hope that a large number of sizable contributions will cancel. Interactions with neutral groups are, in general, short-ranged, with net energy contributions of less than 4 kJ/mol at distances above 5 A from the active site. Interactions with charged groups are much more long-ranged, and interactions with buried charges 20 A from the active site can still contribute by 5 kJ/mol to the reaction energy. Thus, to accurately model the influence of the surroundings on enzyme reaction energies, a detailed and unbiased atomistic account of the surroundings needs to be included.},
  author       = {Hu, LiHong and Eliasson, Jenny and Heimdal, Jimmy and Ryde, Ulf},
  issn         = {1520-5215},
  language     = {eng},
  number       = {43},
  pages        = {11793--11800},
  publisher    = {The American Chemical Society},
  series       = {Journal of physical chemistry. A},
  title        = {Do quantum mechanical energies calculated for small models of protein-active sites converge?},
  url          = {http://dx.doi.org/10.1021/jp9029024},
  volume       = {113},
  year         = {2009},
}