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

Angela M. Barragan, Klaus Schulten, Ilia A. Solov'yov
Journal of Physical Chemistry B
The bc1 complex is a critical enzyme for the ATP production inphotosynthesis 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 Qo-site prior and after the transfers. The analysis of orbitals and partial charge distribution of the
different states of the Qo-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.

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