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Many will enter, few will win: Cost and sensitivity of exploratory dynamics.

Elena F Koslover1, Milo M Lin2, Rob Phillips3

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|September 11, 2025
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Exploratory dynamics in biomolecular systems allow for sensitive responses to parameter changes, but require energy for resetting. This study models ribosome proofreading and microtubule dynamics to balance sensitivity and energy cost.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Biochemistry

Background:

  • Biomolecular systems utilize exploratory dynamics to reach cellular targets.
  • These systems often require resetting transitions to the origin due to lack of direct sensing mechanisms.
  • Exploratory dynamics can lead to enhanced sensitivity to parameter changes but incur energy costs.

Purpose of the Study:

  • To investigate how exploratory dynamics confer functional benefits in biomolecular systems.
  • To analyze the trade-offs between energetic cost and sensitivity in these dynamics.
  • To model translational proofreading and microtubule length control as examples.

Main Methods:

  • Minimalist modeling of biological systems.
  • Application of path-counting and circuit-mapping approaches.
  • Analysis of thermodynamic driving and energy dissipation.

Main Results:

  • Exploratory dynamics enable large shifts in steady-state behavior in response to small parameter changes.
  • Resetting cycles necessitate energy dissipation to move systems from equilibrium.
  • Translational proofreading benefits from driven hydrolysis for substrate discrimination.
  • Microtubule length control utilizes resetting cycles for catalytic regulation.

Conclusions:

  • A limited amount of thermodynamic driving is sufficient for enhanced sensitivity in biomolecular systems.
  • These systems achieve accurate discrimination and catalytic control at a modest energetic cost.
  • Path-counting and circuit-mapping are valuable tools for analyzing futile cycles and steady-state distributions.