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202387 https://hdl.handle.net/2286/R.2.N.202387 http://rightsstatements.org/vocab/InC/1.0/ All Rights Reserved 2025 142 pages Doctoral Dissertation Academic theses en Nguyen, Jonathan Singharoy, Abhishek Fromme, Petra Redding, Kevin Mujica, Vladimiro Arizona State University Partial requirement for: Ph.D., Arizona State University, 2025 Field of study: Biochemistry The products of photosynthesis and respiration drive the vast majority of cellular processes in life. Through the absorption of sunlight, splitting of water molecules, and electron transfer across photosynthetic protein complexes, NADPH is produced. NADPH serves as a key factor in redox reactions in cells, as well as ATP synthesis, the energy currency of life. In nature, overall energy efficiency suffers, due to several bottlenecks encountered during electron transfer. One of the major consequences of these bottlenecks is electrons leaking out of the electron transport chain. These electrons are highly susceptible to being lost to reactive oxygen species (ROS), which ultimately harms the cellular machinery in the organism due to oxidative stress. In order to alleviate this effect, synthetic designs of supercomplexes are proposed. With supercomplexes, tighter protein and lipid interactions are present, creating less distance for electrons to travel. As a result, the rate of electron transfer increases, as well as the rate of overall ATP production. In the following chapters, the biological implications of supercomplexes are invesitgated through theoretical and experimental methods, such as molecular dynamics (MD) cryo-electron microscopy (cryo-EM), and serial femtosecond x-ray crystallography, using x-ray free electron lasers (XFELs). Biochemistry Biophysics Biology Molecular Origins of Biological Energy Transfer Revealed by Synthetic Design of Supercomplexes