How subunit coupling produces the γ-​subunit rotary motion in F1-​ATPase

F0F1-​ATP synthase manufs. the energy "currency,​" ATP, of living cells. The sol. F1 portion, called F1-​ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the γ-​subunit. A coarse-​grained plastic network model is used to show at a residue level of detail how the conformational changes of the catalytic β-​subunits act on the γ-​subunit through repulsive van der Waals interactions to generate a torque that drives unidirectional rotation, as obsd. exptl. The simulations suggest that the calcd. 850 substep rotation is driven primarily by ATP binding and that the subsequent 35° substep rotation is produced by product release from one β-​subunit and a concomitant binding pocket expansion of another β-​subunit. The results of the simulation agree with previously reported single-​mol. expts. and support a tri-​site rotary mechanism for F1-​ATPase under physiol. conditions.