The molecular basis of life is established by a complex membrane-bound protein machinery that efficiently captures chemical and light energy and transduces this into other energy forms. This NAISS project is a continuation of our 2024 Large Computing project in which we studied molecular principles of proteins that catalyze chemical and light-driven energy transduction in cellular respiration and photosynthesis, with exciting results from the last funding round. In this proposal, we tackle these and related bioenergetic systems by multiscale simulations, ranging from hybrid quantum/classical (QM/MM) approaches to classical atomistic and coarse-grained simulations and advanced free energy methods that provide a detailed understanding of the structure, energetics, and dynamics of these proteins on a broad range of timescales and spatial resolutions. The simulations are further integrated and validated by biochemical, biophysical, and structural experiments. The project aims to link the molecular structure and dynamics with the biological function and, based on these, derive a molecular understanding of how enzymes generate electrochemical energy gradients across biological membranes. Our work focuses on 1) mechanisms of long-range redox-coupled proton/ion-transport in the Complex I superfamily; 2) the functional role of membrane-bound bioenergetic enzymes and supercomplexes; 3) the function of light-driven systems involved in photosynthetic energy conversion, and 4) development of integrative methodology for probing principles of charge transfer reactions in (bio)chemical systems. This computational consortium involves around 20 researchers (one professor, one staff scientist, 3 post-docs, 8 PhD students, 4 master students, and several external collaborators) supported by generous grants from the KAW foundation, the Göran Gustafsson Foundation, and VR, with a broad international collaborative network.