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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.
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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.
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- Award ID(s):
- 2102461
- PAR ID:
- 10642483
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Journal of Computational Chemistry
- Volume:
- 46
- Issue:
- 1
- ISSN:
- 0192-8651
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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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
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/jcc.70012
