Period Robustness and Entrainability of the Kai System to Changing Nucleotide Concentrations.

Circadian clocks must be able to entrain to time-varying signals to keep their oscillations in phase with the day-night rhythm. On the other hand, they must also exhibit input compensation: their period must remain approximately one day in different constant environments. The posttranslational oscillator of the Kai system can be entrained by transient or oscillatory changes in the ATP fraction, yet is insensitive to constant changes in this fraction. We study in three different models of this system how these two seemingly conflicting criteria are met. We find that one of these (our recently published Paijmans model) exhibits the best tradeoff between input compensation and entrainability: on the footing of equal phase-response curves, it exhibits the strongest input compensation. Performing stochastic simulations at the level of individual hexamers allows us to identify a new, to our knowledge, mechanism, which is employed by the Paijmans model to achieve input compensation: at lower ATP fraction, the individual hexamers make a shorter cycle in the phosphorylation state space, which compensates for the slower pace at which they traverse the cycle.

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