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

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.