Mechanism of the Primary Charge Transfer Reaction in the Cytochrome bc₁ Complex

The bc₁ complex is a critical enzyme for the ATP production in photosynthesis and cellular respiration. Its biochemical function relies on the so-called Q-cycle, which is well established and operates via quinol substrates that bind inside the protein complex. Despite decades of research, the quinol-protein interaction, which initiates the Q-cycle, has not yet been completely described. Furthermore, the initial charge transfer reactions of the Q-cycle lack a physical description. The present investigation utilizes classical molecular dynamics simulations in tandem with quantum density functional theory calculations, to provide a complete and consistent quantitative description of the primary events that occur within the bc₁ complex upon quinol binding. In particular, the electron and proton transfer reactions that trigger the Q-cycle in the bc₁ complex from Rhodobacter capsulatus are studied. The coupled nature of these charge transfer reactions was revealed by obtaining the transition energy path connecting configurations of the Q_o-site prior and after the transfers. The analysis of orbitals and partial charge distribution of the different states of the Q_o-site has further supported the conclusion. Finally, key structural elements of the bc₁ complex that trigger the charge transfer reactions were established, manifesting the importance of the environment in the process, which is furthermore evidenced by free energy calculations.