Modeling the Energy Landscape of Side Reactions in the Cytochrome bc1 Complex

Husen, Peter; Solov’yov, Ilia A.

doi:10.3389/fchem.2021.643796

Cited by 7 publications

(8 citation statements)

References 56 publications

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“…Recently, significant computational and experimental progress studying electron transfer and subsequent radical-pair dynamics within proteins has been accomplished. ,,− In particular, electron transfer rates and the magnitudes of different interaction terms have been calculated for various biologically relevant radical pairs. Some studies have even spanned wide scales to model the effects of radical-pair interactions on navigation at the organism level .…”

Section: Introductionmentioning

confidence: 99%

Long-Time Oxygen Localization in Electron Transfer Flavoprotein

Salerno

Domenico

et al. 2022

J. Chem. Inf. Model.

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Reactive oxygen species (ROS) exert a wide range of biological effects from beneficial regulatory function to deleterious oxidative stress. The electron transfer flavoprotein (ETF) is ubiquitous to life and is associated with aerobic metabolism and ROS production due to its location in the mitochondria. Quantifying oxygen localization within the ETF complex is critical for understanding the potential for electron transfer and radical pair formation between flavin adenine dinucleotide (FAD) cofactor and superoxide during ROS formation. Our study employed all-atom molecular dynamics simulations and identified several novel, long-lived oxygen binding sites within the ETF complex that appear near the FAD cofactor. Site locations, the local electrostatic environment, and characteristic oxygen binding times for each site were evaluated to establish factors that may lead to possible charge transfer reactions and superoxide formation within the ETF complex. The study revealed that some oxygen binding sites are naturally linked to protein domain features, suggesting opportunities to engineer and control ROS production and subsequent dynamics.

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Section: Introductionmentioning

confidence: 99%

Long-Time Oxygen Localization in Electron Transfer Flavoprotein

Salerno

Domenico

et al. 2022

J. Chem. Inf. Model.

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“…These processes have been speculated to be magnetic-field dependent, which is however outside the scope of the present work . Electron-transfer reactions involving biomacromolecules are commonly modeled by combining Marcus theory calculations with reactant and product state energies computed from molecular dynamics and quantum chemistry models, an approach that we adopt here. ,− …”

Section: Resultsmentioning

confidence: 99%

“…The large-scale protein dynamics can also be important for O 2 binding stability at different sites before and after an electron-transfer reaction. In turn, the stability of the reactant and product states is closely connected to the rate of electron transfer. , Previously, the dynamics of the ETF protein complex was examined in an effort to better understand oxygen binding . ETF is a dimeric protein that comprises three domains, and this structure strongly influences the internal protein dynamics and fluctuations.…”

Section: Resultsmentioning

confidence: 99%

Long-Time Oxygen and Superoxide Localization in Arabidopsis thaliana Cryptochrome

Salerno,

Domenico,

et al. 2023

J. Chem. Inf. Model.

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Cryptochromes are proteins that are highly conserved across species and in many instances bind the flavin adenine dinucleotide (FAD) cofactor within their photolyasehomology region (PHR) domain. The FAD cofactor has multiple redox states that help catalyze reactions, and absorbs photons at about 450 nm, a feature linked to the light-related functions of cryptochrome proteins. Reactive oxygen species (ROS) are produced from redox reactions involving molecular oxygen and are involved in a myriad of biological processes. Superoxide O 2•− is an exemplary ROS that may be formed through electron transfer from FAD to O 2 , generating an electron radical pair. Although the formation of a superoxide−FAD radical pair has been speculated, it is still unclear if the required process steps could be realized in cryptochrome. Here, we present results from molecular dynamics (MD) simulations of oxygen interacting with the PHR domain of Arabidopsis thaliana cryptochrome 1 (AtCRY1). Using MD simulation trajectories, oxygen binding locations are characterized through both the O 2 −FAD intermolecular distance and the local protein environment. Oxygen unbinding times are characterized through replica simulations of the bound oxygen. Simulations reveal that oxygen molecules can localize at certain sites within the cryptochrome protein for tens of nanoseconds, and superoxide molecules can localize for significantly longer. This relatively longduration molecule binding suggests the possibility of an electron-transfer reaction leading to superoxide formation. Estimates of electron-transfer rates using the Marcus theory are performed for the identified potential binding sites. Molecular oxygen binding results are compared with recent results demonstrating long-time oxygen binding within the electron-transfer flavoprotein (ETF), another FAD binding protein.

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“…The computed solvent reorganization energy is of similar magnitude as obtained in previous simulations for the O 2 -to-O − 2 conversion. [36,37]. The reaction energy shows this reaction step is thermodynamically neutral.…”

Section: Resultsmentioning

confidence: 99%

Cation-induced changes in the inner- and outer-sphere mechanisms of electrocatalytic CO2 reduction

Qin

Hansen

Honkala

et al. 2022

Preprint

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The electrocatalytic CO2 reduction reaction (CO2RR) is an attractive approach to produce fuels and chemicals through CO2 recycling and renewable energy. While it is well-known that metal cations greatly affect the CO2RR activity and selectivity, the underlying mechanism remains debated. Herein, we study cation effects on the CO2RR kinetics and thermodynamics over Au by simulating both outer-sphere electron transfer (OS-ET) and inner-sphere electron transfer (IS-ET) pathways during the first CO2 reduction step via advanced constrained density functional theory molecular dynamics (cDFT-MD) simulations and DFT-MD with slow-growth sampling (SG-DFT-MD) technique, respectively. Our computational analysis shows that without any cations only the OS-ET is feasible with a barrier of 1.21 eV. In the presence of K+, OS-ET shows a very high barrier of 2.93 eV and is prohibited by cations. In stark contrast, cations promote the CO2 activation through IS-ET and the barrier for generating adsorbed CO2δ−, the key CO2RR intermediate, is only 0.61 eV. Without cations, CO2-to- CO2δ−(ads) conversion cannot proceed. We also find that the cation effects arise from the short-range Coulomb, ionic-like interactions between cations and reaction intermediates rather than the long-range electrostatic interactions. Overall, our results disclose that cations modulate the inner- and outer-sphere pathways of CO2RR at Au-water interfaces through short-range interactions. These findings provide substantial new insights on the cation specificity in the initial CO2RR steps.

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Modeling the Energy Landscape of Side Reactions in the Cytochrome bc1 Complex

Cited by 7 publications

References 56 publications

Long-Time Oxygen Localization in Electron Transfer Flavoprotein

Long-Time Oxygen Localization in Electron Transfer Flavoprotein

Long-Time Oxygen and Superoxide Localization in Arabidopsis thaliana Cryptochrome

Cation-induced changes in the inner- and outer-sphere mechanisms of electrocatalytic CO2 reduction

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