Attracting oscillations in sequential distributive multisite phosphorylation

The sequential distributive n-site phosphorylation cycle with one kinase and one phosphatase admits attracting positive periodic orbits under mass-action kinetics for every n≥3. An explicit three-site family has a fixed positive equilibrium, a transversal imaginary-eigenvalue crossing, a stable complementary spectrum and a negative first Lyapunov coefficient. A site-addition argument extends the supercritical Hopf bifurcation to every larger site count. Together with the one-site calculation and Vassena's two-site exclusion, this makes three the exact threshold for Hopf bifurcation in this family. Dynamic sequestration of the shared enzymes supplies the feedback: the equilibrium, productive fluxes and statically eliminated vector field remain fixed while stability changes. Further results compare enzyme clamps and selective reduction, quantify flux and amplitude laws, validate two finite-amplitude attracting orbits, and give a driven thermodynamic realization. Exact algebra and interval certificates support the quantitative claims; numerical continuation is distinguished from proof. A registered Lean theorem independently establishes an existential affine family with attracting periodic orbits for every n≥3. The manuscript's arbitrary-parent site-addition theorem and its quantitative extensions go beyond that registered statement.

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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-10-17
DOI
https://doi.org/10.5281/zenodo.23438809
Primary Topic
Advanced Differential Equations and Dynamical Systems
Type
preprint
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preprint

Attracting oscillations in sequential distributive multisite phosphorylation

Michael Mislan
Zenodo (CERN European Organization for Nuclear Research)
Advanced Differential Equations and Dynamical Systems
preprint

Attracting oscillations in sequential distributive multisite phosphorylation

Michael Mislan
preprint en

Abstract

The sequential distributive n-site phosphorylation cycle with one kinase and one phosphatase admits attracting positive periodic orbits under mass-action kinetics for every n≥3. An explicit three-site family has a fixed positive equilibrium, a transversal imaginary-eigenvalue crossing, a stable complementary spectrum and a negative first Lyapunov coefficient. A site-addition argument extends the supercritical Hopf bifurcation to every larger site count. Together with the one-site calculation and Vassena's two-site exclusion, this makes three the exact threshold for Hopf bifurcation in this family. Dynamic sequestration of the shared enzymes supplies the feedback: the equilibrium, productive fluxes and statically eliminated vector field remain fixed while stability changes. Further results compare enzyme clamps and selective reduction, quantify flux and amplitude laws, validate two finite-amplitude attracting orbits, and give a driven thermodynamic realization. Exact algebra and interval certificates support the quantitative claims; numerical continuation is distinguished from proof. A registered Lean theorem independently establishes an existential affine family with attracting periodic orbits for every n≥3. The manuscript's arbitrary-parent site-addition theorem and its quantitative extensions go beyond that registered statement.

Zenodo (CERN European Organization for Nuclear Research)
Advanced Differential Equations and Dynamical Systems
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