title: Exploiting the dynamic properties of covalent modification cycle for the design of synthetic analog biomolecular circuitry.
abstract: BACKGROUND
  Cycles of covalent modification are ubiquitous motifs in cellular signalling. Although such signalling cycles are implemented via a highly concise set of chemical reactions, they have been shown to be capable of producing multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic, signal-transducing and threshold-hyperbolic.
  
  
  RESULTS
  In this paper, we show how the set of chemical reactions underlying covalent modification cycles can be exploited for the design of synthetic analog biomolecular circuitry. We show that biomolecular circuits based on the dynamics of covalent modification cycles allow (a) the computation of nonlinear operators using far fewer chemical reactions than purely abstract designs based on chemical reaction network theory, and (b) the design of nonlinear feedback controllers with strong performance and robustness properties.
  
  
  CONCLUSIONS
  Our designs provide a more efficient route for translation of complex circuits and systems from chemical reactions to DNA strand displacement-based chemistry, thus facilitating their experimental implementation in future Synthetic Biology applications.
authors.affiliation: Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick, Coventry, CV4 7AL UK.
authors.forename: Mathias
authors.identifier: 0000-0003-1400-2659
authors.initials: M
authors.lastname: Foo
authors.affiliation: Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick, Coventry, CV4 7AL UK.
authors.forename: Rucha
authors.initials: R
authors.lastname: Sawlekar
authors.affiliation: Warwick Integrative Synthetic Biology Centre, School of Engineering, University of Warwick, Coventry, CV4 7AL UK.
authors.forename: Declan G
authors.initials: DG
authors.lastname: Bates
keywords: Analog synthetic biomolecular circuits; Chemical reaction networks; Covalent modification cycle; Feedback control systems; Linear and nonlinear operators; Synthetic biology applications