• Bioinformatics, MSc Level
• Structural Biochemistry, MSc Level
• Experimental Chemical Methods, BSc Level
• Molecular Structure and Statistical Thermodynamics, BSc Level
• Mathematical Methods in Chemistry, BSc Level

• Computational Multi-Scale Simulations of Biological Energy Conversion
• Proton Transfer Mechanisms in Respiratory Complex I

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• Functional Water Wires Catalyze Long-Range Proton Pumping in the Mammalian Respiratory Complex I

  2020. Michael Röpke (et al.). Journal of the American Chemical Society 142 (52), 21758-21766

  Article

  The respiratory complex I is a gigantic (1 MDa) redox-driven proton pump that reduces the ubiquinone pool and generates proton motive force to power ATP synthesis in mitochondria. Despite resolved molecular structures and biochemical characterization of the enzyme from multiple organisms, its long-range (similar to 300 A) proton-coupled electron transfer (PCET) mechanism remains unsolved. We employ here microsecond molecular dynamics simulations to probe the dynamics of the mammalian complex I in combination with hybrid quantum/classical (QM/MM) free energy calculations to explore how proton pumping reactions are triggered within its 200 A wide membrane domain. Our simulations predict extensive hydration dynamics of the antiporter-like subunits in complex I that enable lateral proton transfer reactions on a microsecond time scale. We further show how the coupling between conserved ion pairs and charged residues modulate the proton transfer dynamics, and how transmembrane helices and gating residues control the hydration process. Our findings suggest that the mammalian complex I pumps protons by tightly linked conformational and electrostatic coupling principles.

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Show all publications by Maximilian Pöverlein at Stockholm University