Mechanistic Bioenergetics and Computational Biochemistry

Our goal is to elucidate the mechanistic principles of biological energy conversion. To this end, we develop integrative biophysical methods that allow us to unravel how the catalytic power of enzymes arises from their structure, conformational dynamics, and biological surroundings.

Life is powered by a membrane-bound protein machinery that captures chemical and light energy to sustain the energy metabolism of our cells. At a molecular level, these processes are catalyzed by highly efficient protein complexes that transport charge (protons, ions, and electrons) across large molecular distances at remarkable catalytic efficiencies. Yet, despite recent structural advances, the mechanistic principles of these processes remain poorly understood and much debated. Our research aims to decipher the molecular mechanisms by which bioenergetic enzyme complexes catalyze long-range charge transport to power the cellular energy catalysis, and how their dysfunction results in human diseases. To address these challenging questions, we develop integrative biophysical approaches that combine powerful multiscale simulations and data-driven approaches with biochemical and structural experiments. Our multidisciplinary approach allows us to probe the energetics, dynamics, and functional principles on a broad range of timescales and spatial resolutions, and to rationally test mechanistic hypotheses in both natural and synthetic model systems.

See extended description here.

Selected publications

• Kim H et al. (2023). Quinone Catalysis Modulates Proton Transfer Reactions in the Membrane–Domain of Respiratory Complex I. JACS 145: 17075-17086.
• Saura P et al. (2022). Electric Fields Control Water-Gated Proton Transfer in Cytochrome c Oxidase. PNAS 119(38): e2207761119.
• Allgöwer F et al. (2022).Molecular Principles of Redox-Coupled Protonation Dynamics in Photosystem II. JACS 144: 7171-7180.
• Röpke M et al. (2021) Deactivation blocks proton pathways in the mitochondrial complex I. PNAS 118: e2019498118.
• Baumgart M et al. (2021) Design of buried ion-pairs in artificial proteins. Nature Comms 12: 1895, 1-10.
• Kaila VRI (2021)Architecture of Bacterial Respiratory Chains. Nature Rev Microbiol 19: 319-330.
• Bridges HR et al. (2020) Structure of inhibitor-bound mammalian complex I, Nature Comms, 5261: 11, 1-11.
• Schuller JM et al. (2020) Redox-Coupled Proton Pumping Drives Carbon Concentration in the Photosynthetic Complex I, Nature Comms 11: 494, 1-7.
• Mühlbauer ME et al. (2020) Water-gated proton transfer dynamics in respiratory complex I. JACS 142, 13718-13728.
• Mader SL et al.(2020)Conformational dynamics modulate the catalytic activity of the molecular chaperone Hsp90. Nature Comms 11: 11410, 1-12.