An official website of the United States government
Abstract For a series of cytochrome b5 proteins isolated from various species, including bacteria, animals, and humans, we analyzed the intrinsic strength of their distal/proximal FeN bonds and the intrinsic stiffness of their axial NFeN bond angles. To assess intrinsic bond strength and bond angle stiffness, we employed local vibrational stretching force constants ka(FeN) and bending force constants ka(NFeN) derived from the local mode theory developed by our group; the ferric and ferrous oxidation states of the heme Fe were considered. All calculations were conducted with the QM/MM methodology. We found that the reduction of the heme Fe from the ferric to the ferrous state makes the FeN axial bonds weaker, longer, less covalent, and less polar. Additionally, the axial NFeN bond angle becomes stiffer and less flexible. Local mode force constants turned out to be far more sensitive to the protein environment than geometries; evaluating force constant trends across diverse protein groups and monitoring changes in the axial heme‐framework revealed redox‐induced changes to the primary coordination sphere of the protein. These results indicate that local mode force constants can serve as useful feature data for training machine learning models that predict cytochrome b5 redox potentials, which currently rely more on geometric data and qualitative descriptors of the protein environment. The insights gained through our investigation also offer valuable guidance for strategically fine‐tuning artificial cytochrome b5 proteins and designing new, versatile variants.
more »
« less
A Closer Look at the FeS Heme Bonds in Azotobacter vinelandii Bacterioferritin: QM/MM and Local Mode Analysis
ABSTRACT Using the QM/MM methodology and a local mode analysis, we investigated a character and a strength of FeS bonds of heme groups in oxidized and reduced forms of Bacterioferritin fromAzotobacter vinelandii. The strength of the FeS bonds was correlated with a bond length, an energy density at a bond critical point, and a charge difference of the F and S atoms. Changing the oxidation state from ferrous to ferric generally makes the FeS bonds weaker, longer, more covalent, and more polar. We also investigated the SFeS bond bending and found that the stronger FeS bond, generally makes the SFeS bond bending stiffer, which could play a key role in the balance between ferric and ferrous oxidation states and related biological activities.
more »
« less
- Award ID(s):
- 2102461
- PAR ID:
- 10564598
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Journal of Computational Chemistry
- Volume:
- 46
- Issue:
- 1
- ISSN:
- 0192-8651
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract We investigated the intrinsic strength of distal and proximal FeN bonds for both ferric and ferrous oxidation states of bishistidyl hemoproteins from bacteria, animals, human, and plants, including two cytoglobins, ten hemoglobins, two myoglobins, six neuroglobins, and six phytoglobins. As a qualified measure of bond strength, we used local vibrational force constants k(FeN) based on local mode theory developed in our group. All calculations were performed with a hybrid QM/MM ansatz. Starting geometries were taken from available x‐ray structures. k(FeN) values were correlated with FeN bond lengths and covalent bond character. We also investigated the stiffness of the axial NFeN bond angle. Our results highlight that protein effects are sensitively reflected in k(FeN), allowing one to compare trends in diverse protein groups. Moreover, k(NFeN) is a perfect tool to monitor changes in the axial heme framework caused by different protein environments as well as different Fe oxidation states.more » « less
-
null (Ed.)Nitrosoarenes (ArNOs) are toxic metabolic intermediates that bind to heme proteins to inhibit their functions. Although much of their biological functions involve coordination to the Fe centers of hemes, the factors that determine N-binding or O-binding of these ArNOs have not been determined. We utilize X-ray crystallography and density functional theory (DFT) analyses of new representative ferrous and ferric ArNO compounds to provide the first theoretical insight into preferential N-binding versus O-binding of ArNOs to hemes. Our X-ray structural results favored N-binding of ArNO to ferrous heme centers, and O-binding to ferric hemes. Results of the DFT calculations rationalize this preferential binding on the basis of the energies of associated spin-states, and reveal that the dominant stabilization forces in the observed ferrous N-coordination and ferric O-coordination are dπ–pπ* and dσ–pπ*, respectively. Our results provide, for the first time, an explanation why in situ oxidation of the ferrous-ArNO compound to its ferric state results in the observed subsequent dissociation of the ligand.more » « less
-
Under anaerobic conditions, ferrous iron reacts with sulfide producing FeS, which can then undergo a temperature, redox potential, and pH dependent maturation process resulting in the formation of oxidized mineral phases, such as greigite or pyrite. A greater understanding of this maturation process holds promise for the development of iron-sulfide catalysts, which are known to promote diverse chemical reactions, such as H + , CO 2 and NO 3 − reduction processes. Hampering the full realization of the catalytic potential of FeS, however, is an incomplete knowledge of the molecular and redox processess ocurring between mineral and nanoparticulate phases. Here, we investigated the chemical properties of iron-sulfide by cyclic voltammetry, Raman and X-ray absorption spectroscopic techniques. Tracing oxidative maturation pathways by varying electrode potential, nanoparticulate n (Fe 2+ S 2− ) (s) was found to oxidize to a Fe 3+ containing FeS phase at −0.5 V vs. Ag/AgCl (pH = 7). In a subsequent oxidation, polysulfides are proposed to give a material that is composed of Fe 2+ , Fe 3+ , S 2− and polysulfide (S n 2− ) species, with its composition described as Fe 2+ 1−3 x Fe 3+ 2 x S 2− 1− y (S n 2− ) y . Thermodynamic properties of model compounds calculated by density functional theory indicate that ligand oxidation occurs in conjunction with structural rearrangements, whereas metal oxidation may occur prior to structural rearrangement. These findings together point to the existence of a metastable FeS phase located at the junction of a metal-based oxidation path between FeS and greigite (Fe 2+ Fe 3+ 2 S 2− 4 ) and a ligand-based oxidation path between FeS and pyrite (Fe 2+ (S 2 ) 2− ).more » « less
-
In this work, we analyzed five groups of different dihydrogen bonding interactions and hydrogen clusters with an H3+ kernel utilizing the local vibrational mode theory, developed by our group, complemented with the Quantum Theory of Atoms–in–Molecules analysis to assess the strength and nature of the dihydrogen bonds in these systems. We could show that the intrinsic strength of the dihydrogen bonds investigated is primarily related to the protonic bond as opposed to the hydridic bond; thus, this should be the region of focus when designing dihydrogen bonded complexes with a particular strength. We could also show that the popular discussion of the blue/red shifts of dihydrogen bonding based on the normal mode frequencies is hampered from mode–mode coupling and that a blue/red shift discussion based on local mode frequencies is more meaningful. Based on the bond analysis of the H3+(H2)n systems, we conclude that the bond strength in these crystal–like structures makes them interesting for potential hydrogen storage applications.more » « less
