Not yet reviewed by Pith; the record is open.

Living systems at the molecular scale are composed of many constituents with strong and heterogeneous interactions, operating far from equilibrium, and subject to strong fluctuations. These conditions pose 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 the ingenious rotary machine FoF1-ATP synthase, we investigate the interplay between nonequilibrium driving forces, thermal fluctuations, and interactions between strongly coupled subsystems. This model reveals design principles for effective free energy transduction. Most notably, while tight coupling is intuitively appealing, we find that output power is maximized at intermediate-strength coupling, which permits lubrication by stochastic fluctuations with only minimal slippage.