Dissertation
Computational Studies of the Reaction Mechanisms Of Methyl Coenzyme M Reductase, [FeFe]-Hydrogenase And Rh-LmrR
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000005041
Abstract
Enzymes are proteins that are Nature’s catalysts and have evolved to catalyze some of the most energy-demanding reactions in nature. Their evolutionary advantage has allowed them to employ mechanisms that are much more efficient and inexpensive than current industrial processes. Because of this, understanding how enzymes work is critical in the development of better catalytic processes. In the work reported here, I will focus on studies on enzymatic mechanisms using computational chemistry tools, demonstrating how different aspects of the complexity imposed by the enzyme can be studied at different scales. The importance of these three systems lies in their ability to facilitate reactions that are critical in energy applications: [FeFe]-Hydrogenase is an enzyme that reversibly and efficiently interconverts protons (H+) and electrons (e−) to molecular hydrogen (H2); Methyl Coenzyme-M Reduc- tase (MCR) is the enzyme responsible for methane formation and oxidation; the Rh-LmrR artificial enzyme is able to hydrogenate CO2 to formate (HCOO−). This work highlights several different aspects of how the protein environment in enzymes beyond the active site modulates different aspects of the catalytic mechanisms. In MCR, the protein environment assists in the positioning of substrates in the active site pocket, revealing the possibility of an alternative mechanism that eliminates the need for the rearrangement of substrates. In [FeFe]-Hydrogenase the protein environment modulates the catalytic bias by stabilizing the desired electronic states of the cofactors and influences activity by changing the ability of the protein transport network to move protons via a thermodynamic gradient. Finally, in the artificial enzyme Rh-LmrR we reveal how the dynamics of both the scaffold and the solvent can influence activity by modulating the electronic environment in the active site, the delivery of the CO2 substrate, and changing the access to water. Collectively, these studies demonstrated the importance of carefully considering the role of the broader protein and solvent environment and the need to incorporate some of these features as transferable design principles in the development of synthetic catalysts for energy applications.
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Details
- Title
- Computational Studies of the Reaction Mechanisms Of Methyl Coenzyme M Reductase, [FeFe]-Hydrogenase And Rh-LmrR
- Creators
- Bojana Ginovska
- Contributors
- Aurora E Clark (Advisor)Gregory K Schenter (Committee Member)John W Peters (Committee Member)James A Brozik (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Mechanical and Materials Engineering
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 206
- Identifiers
- 99901019232601842
- Language
- English
- Resource Type
- Dissertation