Energy-speed-accuracy relation in complex networks for biological discrimination

Discriminating between correct and incorrect substrates is a core process in biology, but how is energy apportioned between the conflicting demands of accuracy (mu), speed (sigma), and total entropy production rate (P)? Previous studies have focused on biochemical networks with simple structure or relied on simplifying kinetic assumptions. Here, we use the linear framework for timescale separation to analytically examine steady-state probabilities away from thermodynamic equilibrium for networks of arbitrary complexity. We also introduce a method of scaling parameters that is inspired by Hopfield's treatment of kinetic proofreading. Scaling allows asymptotic exploration of high-dimensional parameter spaces. We identify in this way a broad class of complex networks and scalings for which the quantity sigma ln(mu)/P remains asymptotically finite whenever accuracy improves from equilibrium, so that mu(eq)/mu -> 0. Scalings exist, however, even for Hopfield's original network, for which sigma ln(mu)/P is asymptotically infinite, illustrating the parametric complexity. Outside the asymptotic regime, numerical calculations suggest that, under more restrictive parametric assumptions, networks satisfy the bound, sigma ln(mu/mu(eq))/P < 1, and we discuss the biological implications for discrimination by ribosomes and DNA polymerase. The methods introduced here may be more broadly useful for analyzing complex networks that implement other forms of cellular information processing.