Simulating the Coupling of Catalysis and Electron Transfer along Chains of FeS-Clusters in Various Enzymes

• Applicant: Professor Dr. Matthias Ullmann
• Subject Area: Biophysics ; Bioinformatics and Theoretical Biology ; Structural Biology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 311144407

Iron-sulfur clusters play central role in many long range electron transfer processes ranging from functions in molecular bioenergetic, in enzyme catalysis, as well as in gene regulation and repair. In many of these enzymes, iron sulfur clusters align to enable electron transfer over large distances. Prominent examples of such enzymes are molybdo- and tungsto-pterin enzymes but also several hydrogenases. While the catalytic reactions of many of these enzymes have been investigated at quite some detail, their connection to the electron and proton transfer reactions has not been studied at the same level of detail. The goal of this project is to extend an existing method for electron and proton transfer simulation to describe the coupling of catalytic reactions and charge transfer reactions between catalytic sites in enzymes. We will use the master equation approach for simulating reactions in using the microstate model. For these calculations, it is required to calculate reaction rate constants. For electron and proton transfer reactions, we estimate these rate constants using Marcus theory. The driving force of these reaction is obtained from the difference of the microstate energies. For more complex chemical reactions, we will employ QM/MM calculations. In order to calculate microstate energies of protein containing FeS clusters, we need to estimate reliable model redox potentials for these clusters. Therefore, the properties of the most common FeS clusters involved in electron transfer will be investigated. The simulation method will be applied to analyze the reaction of two F420-reducing and one NAD reducing hydrogenases, which are similar to each other, but show interesting differences. Our simulating can show how the pH and the solution redox potential influence the reduction level of the enzyme and how the redox state of the enzyme is connected to the overall flux through the enzyme.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1927: Iron-Sulfur for Life