Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations
Cao, Lili LU ; Caldararu, Octav LU and Ryde, Ulf LU
(2018)
In Journal of Chemical Theory and Computation
14(12).
p.6653-6678
- Abstract
We have performed a systematic computational study of the relative energies of possible protonation states of the FeMo cluster in nitrogenase in the E0-E4 states, i.e., the resting state and states with 1-4 electrons and protons added but before N2 binds. We use the combined quantum mechanics and molecular mechanics (QM/MM) approach, including the complete solvated heterotetrameric enzyme in the calculations. The QM system consisted of 112 atoms, i.e., the full FeMo cluster, as well all groups forming hydrogen bonds to it within 3.5 Å. It was treated with either the TPSS-D3 or B3LYP-D3 methods with the def2-SV(P) or def2-TZVPD basis sets. For each redox state, we calculated relative energies of at least... (More)
We have performed a systematic computational study of the relative energies of possible protonation states of the FeMo cluster in nitrogenase in the E0-E4 states, i.e., the resting state and states with 1-4 electrons and protons added but before N2 binds. We use the combined quantum mechanics and molecular mechanics (QM/MM) approach, including the complete solvated heterotetrameric enzyme in the calculations. The QM system consisted of 112 atoms, i.e., the full FeMo cluster, as well all groups forming hydrogen bonds to it within 3.5 Å. It was treated with either the TPSS-D3 or B3LYP-D3 methods with the def2-SV(P) or def2-TZVPD basis sets. For each redox state, we calculated relative energies of at least 50 different possible positions for the proton, added to the most stable protonation state of the level with one electron less. We show quite conclusively that the resting E0 state is not protonated using quantum refinement and by comparing geometries to the crystal structure. The E1 state is protonated on S2B, in agreement with most previous computational studies. However, for the E2-E4 states, the two QM methods give diverging results, with relative energies that differ by over 300 kJ/mol for the most stable E4 states. TPSS favors hydride ions binding to the Fe ions. The first bridges Fe2 and Fe6, whereas the next two bind terminally to either Fe4, Fe5, or Fe6 with nearly equal energies. On the other hand, B3LYP disfavors hydride ions and instead suggests that 1-3 protons bind to the central carbide ion.
(Less)
- author
- Cao, Lili
LU
; Caldararu, Octav
LU
and Ryde, Ulf
LU
- organization
- publishing date
- 2018
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Chemical Theory and Computation
- volume
- 14
- issue
- 12
- pages
- 26 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:30354152
- scopus:85058304021
- ISSN
- 1549-9618
- DOI
- 10.1021/acs.jctc.8b00778
- project
- Computational Studies of Nitrogenase
- language
- English
- LU publication?
- yes
- id
- cda210f7-db3f-4f0c-9d31-846094e9d0e6
- date added to LUP
- 2019-01-03 12:21:54
- date last changed
- 2024-07-10 05:53:30
@article{cda210f7-db3f-4f0c-9d31-846094e9d0e6,
abstract = {{<p>We have performed a systematic computational study of the relative energies of possible protonation states of the FeMo cluster in nitrogenase in the E<sub>0</sub>-E<sub>4</sub> states, i.e., the resting state and states with 1-4 electrons and protons added but before N<sub>2</sub> binds. We use the combined quantum mechanics and molecular mechanics (QM/MM) approach, including the complete solvated heterotetrameric enzyme in the calculations. The QM system consisted of 112 atoms, i.e., the full FeMo cluster, as well all groups forming hydrogen bonds to it within 3.5 Å. It was treated with either the TPSS-D3 or B3LYP-D3 methods with the def2-SV(P) or def2-TZVPD basis sets. For each redox state, we calculated relative energies of at least 50 different possible positions for the proton, added to the most stable protonation state of the level with one electron less. We show quite conclusively that the resting E<sub>0</sub> state is not protonated using quantum refinement and by comparing geometries to the crystal structure. The E<sub>1</sub> state is protonated on S2B, in agreement with most previous computational studies. However, for the E<sub>2</sub>-E<sub>4</sub> states, the two QM methods give diverging results, with relative energies that differ by over 300 kJ/mol for the most stable E<sub>4</sub> states. TPSS favors hydride ions binding to the Fe ions. The first bridges Fe2 and Fe6, whereas the next two bind terminally to either Fe4, Fe5, or Fe6 with nearly equal energies. On the other hand, B3LYP disfavors hydride ions and instead suggests that 1-3 protons bind to the central carbide ion.</p>}},
author = {{Cao, Lili and Caldararu, Octav and Ryde, Ulf}},
issn = {{1549-9618}},
language = {{eng}},
number = {{12}},
pages = {{6653--6678}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Chemical Theory and Computation}},
title = {{Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations}},
url = {{https://lup.lub.lu.se/search/files/57285245/243_prot.pdf}},
doi = {{10.1021/acs.jctc.8b00778}},
volume = {{14}},
year = {{2018}},
}