QM/MM Study of Partial Dissociation of S2B for the E2 Intermediate of Nitrogenase
Jiang, Hao LU
; Svensson, Oskar K. G.
LU
and Ryde, Ulf
LU
(2022)
In Inorganic Chemistry
61(45).
p.18067-18076
- Abstract
- Nitrogenase is the only enzyme that can cleave the triple bond in N2,
making nitrogen available for all lifeforms. Previous computational
studies have given widely diverging results regarding the reaction
mechanism of the enzyme. For example, some recent studies have suggested
that one of the μ2-bridging sulfide ligands (S2B) may dissociate from one of the Fe ions when protonated in the doubly reduced and protonated E2
state, whereas other studies indicated that such half-dissociated
states are unfavorable. We have examined how the relative energies of 26
structures of the E2 state depend on details of combined
quantum mechanical and molecular mechanical... (More) - Nitrogenase is the only enzyme that can cleave the triple bond in N2,
making nitrogen available for all lifeforms. Previous computational
studies have given widely diverging results regarding the reaction
mechanism of the enzyme. For example, some recent studies have suggested
that one of the μ2-bridging sulfide ligands (S2B) may dissociate from one of the Fe ions when protonated in the doubly reduced and protonated E2
state, whereas other studies indicated that such half-dissociated
states are unfavorable. We have examined how the relative energies of 26
structures of the E2 state depend on details of combined
quantum mechanical and molecular mechanical (QM/MM) calculations. We
show that the selection of the broken-symmetry state, the basis set,
relativistic effects, the size of the QM system, relaxation of the
surroundings, and the conformations of the bound protons may affect the
relative energies of the various structures by up to 12, 22, 9, 20, 37,
and 33 kJ/mol, respectively. However, they do not change the preferred
type of structures. On the other hand, the choice of the DFT functional
strongly affects the preferences. The hybrid B3LYP functional strongly
prefers doubly protonation of the central carbide ion, but such a
structure is not consistent with experimental EPR data. Other
functionals suggest structures with a hydride ion, in agreement with the
experiments, and show that the ion bridges between Fe2 and Fe6.
Moreover, there are two structures of the same type that are degenerate
within 1–5 kJ/mol, in agreement with the observation of two EPR signals.
However, the pure generalized gradient approximation (GGA) functional
TPSS favors structures with a protonated S2B also bridging Fe2 and Fe6,
whereas r2SCAN (meta-GGA) and TPSSh (hybrid) prefer
structures with S2B dissociated from Fe2 (but remaining bound to Fe6).
The energy difference between the two types of structure is so small
(7–18 kJ/mol) that both types need to be considered in future
investigations of the mechanism of nitrogenase. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4eb73786-9a09-484a-9577-e7d447e98a68
- author
- Jiang, Hao
LU
; Svensson, Oskar K. G.
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2022-10-28
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- nitrogenase, QM/MM, DFT methods, E2 state, protonation, S2B dissociation
- in
- Inorganic Chemistry
- volume
- 61
- issue
- 45
- pages
- 10 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:36306385
- scopus:85141625051
- ISSN
- 1520-510X
- DOI
- 10.1021/acs.inorgchem.2c02488
- language
- English
- LU publication?
- yes
- id
- 4eb73786-9a09-484a-9577-e7d447e98a68
- date added to LUP
- 2022-11-24 12:46:48
- date last changed
- 2025-10-14 13:13:27
@article{4eb73786-9a09-484a-9577-e7d447e98a68,
abstract = {{Nitrogenase is the only enzyme that can cleave the triple bond in N<sub>2</sub>,<br>
making nitrogen available for all lifeforms. Previous computational <br>
studies have given widely diverging results regarding the reaction <br>
mechanism of the enzyme. For example, some recent studies have suggested<br>
that one of the μ<sub>2</sub>-bridging sulfide ligands (S2B) may dissociate from one of the Fe ions when protonated in the doubly reduced and protonated E<sub>2</sub><br>
state, whereas other studies indicated that such half-dissociated <br>
states are unfavorable. We have examined how the relative energies of 26<br>
structures of the E<sub>2</sub> state depend on details of combined <br>
quantum mechanical and molecular mechanical (QM/MM) calculations. We <br>
show that the selection of the broken-symmetry state, the basis set, <br>
relativistic effects, the size of the QM system, relaxation of the <br>
surroundings, and the conformations of the bound protons may affect the <br>
relative energies of the various structures by up to 12, 22, 9, 20, 37, <br>
and 33 kJ/mol, respectively. However, they do not change the preferred <br>
type of structures. On the other hand, the choice of the DFT functional <br>
strongly affects the preferences. The hybrid B3LYP functional strongly <br>
prefers doubly protonation of the central carbide ion, but such a <br>
structure is not consistent with experimental EPR data. Other <br>
functionals suggest structures with a hydride ion, in agreement with the<br>
experiments, and show that the ion bridges between Fe2 and Fe6. <br>
Moreover, there are two structures of the same type that are degenerate <br>
within 1–5 kJ/mol, in agreement with the observation of two EPR signals.<br>
However, the pure generalized gradient approximation (GGA) functional <br>
TPSS favors structures with a protonated S2B also bridging Fe2 and Fe6, <br>
whereas r<sup>2</sup>SCAN (meta-GGA) and TPSSh (hybrid) prefer <br>
structures with S2B dissociated from Fe2 (but remaining bound to Fe6). <br>
The energy difference between the two types of structure is so small <br>
(7–18 kJ/mol) that both types need to be considered in future <br>
investigations of the mechanism of nitrogenase.}},
author = {{Jiang, Hao and Svensson, Oskar K. G. and Ryde, Ulf}},
issn = {{1520-510X}},
keywords = {{nitrogenase; QM/MM; DFT methods; E2 state; protonation; S2B dissociation}},
language = {{eng}},
month = {{10}},
number = {{45}},
pages = {{18067--18076}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Inorganic Chemistry}},
title = {{QM/MM Study of Partial Dissociation of S2B for the E<sub>2</sub> Intermediate of Nitrogenase}},
url = {{http://dx.doi.org/10.1021/acs.inorgchem.2c02488}},
doi = {{10.1021/acs.inorgchem.2c02488}},
volume = {{61}},
year = {{2022}},
}