Abstract

A dynamical system entrains to a periodic input if its state converges globally to an attractor with the same period. In particular, for a constant input, the state converges to a unique equilibrium point for any initial condition. We consider the problem of maximizing a weighted average of the system’s output along the periodic attractor. The gain of entrainment is the benefit achieved by using a non-constant periodic input relative to a constant input with the same time average. Such a problem amounts to optimal allocation of resources in a periodic manner. We formulate this problem as a periodic optimal control problem, which can be analysed by means of the Pontryagin maximum principle or solved numerically via powerful software packages. We then apply our framework to a class of nonlinear occupancy models that appear frequently in biological synthesis systems and other applications. We show that, perhaps surprisingly, constant inputs are optimal for various architectures. This suggests that the presence of non-constant periodic signals, which frequently appear in biological occupancy systems, is a signature of an underlying time-varying objective functional being optimized.

Highlights

  • Periodic oscillations are abundant in biomolecular systems, and an extensive body of research has been devoted to study their roles in royalsocietypublishing.org/journal/rsos R

  • Such clocks are important in biology, as they allow organisms to adequately respond to periodic processes like the solar day and the cell cycle division process

  • They are essential for synthetic biology, as a common clock is an important ingredient in building synthetic biology circuits that include several modules working in synchrony

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Summary

Introduction

Periodic oscillations are abundant in biomolecular systems, and an extensive body of research has been devoted to study their roles in royalsocietypublishing.org/journal/rsos R. The cell cycle is a periodic routine that regulates DNA replication and cell division This requires precise regulation of many interacting proteins and appropriate resource allocation at different stages of the cell cycle. One biological mechanism for cell cycle-regulated genes is based on codons whose corresponding tRNAs have low abundances (known as non-optimal codons) [14,15]. Our focus is to analyse these models in the presence of periodic excitations modelled as periodic inputs that attempt to maximize a certain reward function that is proportional to the throughput of the system We pose these problems in the rigorous language of optimal control theory and analyse them under a variety of assumptions

Motivation: occupancy models
A one-dimensional model
Multisite models: the ribosome flow model
Generalized occupancy models
Gain of entrainment
Optimal control formulation
Pontryagin’s maximum principle
Application of the Pontryagin maximum principle
Constant controls satisfy the Pontryagin maximum principle
Extremal analysis of the one-dimensional unweighted problem
Gain of entrainment with time-varying weight functions
Unweighted objective functional
Weighted objective functional
Discussion
Analysis of the switching functions
Characterization of singular arcs
Findings
Inadmissibility of regular arcs
Full Text
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