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Biological machines like molecular motors and enzymes operate in dynamic cycles representable as stochastic flows on networks. Current stochastic dynamics describes such flows on fixed networks. Here, we develop a scalable approach to network design in which local transition rates can be systematically varied to achieve global dynamical objectives. It is based on the fluctuation-response duality in the recent Caliber Force Theory – a path-entropy variational formalism for nonequilibria. This approach scales efficiently with network complexity and gives new insights, for example revealing the transition from timing- to branching-dominated fluctuations in a kinesin motor model.

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