Circadian Clock Model with Sequestration Repression Motif: Existence of Periodic Orbits and Entrainment Properties

Abstract

Protein sequestration motifs appear in many biological regulatory networks and introduce special properties into the network dynamics. Sequestration can be described as a mode of inactivation of a given protein by its binding to a second protein to form a new complex. In this complexed form, the original protein is prevented from performing its specific functions and is thus rendered inactive. We study a mathematical model of the mammalian circadian clock with a protein sequestration motif, which generates one of the negative feedback loops that guarantees periodic behavior. First, the motif permits a time-scale separation, which can be used to simplify the model. We show that the simplified model admits a periodic orbit over a fairly large region of parameters. Second, we are able to show that the sequestration motif induces a phase response curve with a very specific form, implying that external perturbations can affect the system only in a narrow window of the periodic orbit. Finally, we compare our model with a classic Goodwin oscillator, to illustrate the dynamical and robustness properties induced by the protein sequestration motif.