Structure of the F o /V o -hybrid ATP synthase rotor ring from Acetobacterium woodii at 2.4 Å resolution

Energetic status of the cell is one the most important factors of its normal physiological functioning. Meanwhile its experimental evaluation is not always possible and reasonable due to high costs and invasiveness. Theoretical description of ATP production in the cell can be possible using existing data about the structure, functioning and spatial distribution of energoproducing systems. The FoF1ATPsynthase is one of the key enzymes in energy supplying in almost all living systems. This enzyme is an attractive research target due to its high mechanical complexity. Nevertheless, some key issues regarding energy conversation during the FoF1-ATPsynthase catalytic cycle are still unclear. The issue of rotational catalysis convertibility arises in the step that describes the rotormovement and proton translocation. This is one of the features that causes difficulty in the creation of a universal model of ATP synthesis. In this work, we provide a theoretical description of FoF1ATPsynthase catalytic cycle using combined mathematical approaches. Thus, the mechanism of Fo can be nominally described as the complexity of the rotation of protein subunits and proton translocation through membrane half-channels, which is an obligatory step in the transformation of the accumulated energy. The description of the above processes can yield the time of proton translocation and the mechanism of energy transformation and its transition to ATP-binding sites. Langevin dynamics is used for the rotation of the central protein core and the Monte-Carlo method helps to model nucleotide and proton binding. This approach is the first in which both ATP synthesis and hydrolysis can occur depending on the nucleotide concentration and system conditions. The calculated rates are close to the experimentally measured rates of ATP functioning. The model has been formalized as a computer simulation Program of ATP Synthesis and Hydrolysis (PASH) that allows researchers to evaluate ATP production both for one enzyme and for dirrefent types of cells. Flexibility of parameter settings in synthesis and hydrolysis of active enzymes and their regulation allows universal application of this approach in the evaluation of cell energetic status.