Molecular dynamics simulations of F1-ATPase

F1-ATPase is a rotary motor enzyme. Despite many theoretical and experimental studies, the molecular mechanism of the motor rotation is still not fully understood. However, plenty of available data provide a clue as to how this molecular motor rotates: with nucleotide perturbations, the catalytically active β subunit propagates its structural changes to the entire α3β3 complex via both sides of the subunits, resulting that asymmetry is created in the α3β3 hexamer ring. In the sequential reaction step, the structure of the asymmetrical α3β3 complex changes from one state to the other due to the nucleotide perturbations, and the γ subunit axis follows the sequentially changing α3β3 structure. Therefore, there are mainly two essential elements for motor rotation: the conformational change of the β subunit and the asymmetrical structure of the α3β3 subunit complex. Therefore, this chapter reports a series of studies focused on these two elements via combinational approaches of molecular dynamics (MD) simulations and experimental or other theoretical studies. In addition to the motor rotation factors, the combined study also revealed other important elements of F1-ATPase, such as torque transmission and the chemical reaction pathway, which is described in the later part of this chapter. All of these results provide insight into the rotational mechanism and deepen the understanding of this molecular motor.