Non-equilibrium response of a strongly coupled rotary motor

Living systems at the molecular scale are complex (composed of many constituents with strong and heterogeneous interactions), far from equilibrium, and subject to strong fluctuations. This poses significant challenges to efficient, precise, and rapid free energy transduction, yet nature has evolved numerous molecular machines that do just this. Using a simple model of FoF1-ATP synthase (the primary motor for ATP synthesis), we investigate the interplay between non-equilibrium driving forces, natural equilibrium fluctuations, and interactions between the strongly coupled subsystems of this ingenious rotary machine. Additionally, we consider the resulting design principles for effective free energy transduction. Most notably, while one would naively assume that tight coupling between subsystems is preferred, we find that the output power is maximized at intermediate-strength coupling, which permits lubrication by stochastic fluctuations with only minimal slippage.