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Main Authors: Koslover, Elena F, Lin, Milo M, Phillips, Rob
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2506.00775
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author Koslover, Elena F
Lin, Milo M
Phillips, Rob
author_facet Koslover, Elena F
Lin, Milo M
Phillips, Rob
contents A variety of biomolecular systems rely on exploratory dynamics to reach target locations or states within a cell. Without a mechanism to remotely sense and move directly towards a target, the system must sample over many paths, often including resetting transitions back to the origin. We investigate how exploratory dynamics can confer an important functional benefit: the ability to respond to small changes in parameters with large shifts in the steady-state behavior. However, such enhanced sensitivity comes at a cost: resetting cycles require energy dissipation in order to push the system out of its equilibrium steady state. We focus on minimalist models for two concrete examples: translational proofreading in the ribosome and microtubule length control via dynamic instability to illustrate the trade-offs between energetic cost and sensitivity. In the former, a driven hydrolysis step enhances the ability to distinguish between substrates and decoys with small binding energy differences. In the latter, resetting cycles enable catalytic control, with the steady-state length distribution modulated by sub-stoichiometric concentrations of a reusable catalyst. Synthesizing past models of these well-studied systems, we show how path-counting and circuit mapping approaches can be used to address fundamental questions such as the number of futile cycles inherent in translation and the steady-state length distribution of a dynamically unstable polymer. In both cases, a limited amount of thermodynamic driving is sufficient to yield a qualitative transition to a system with enhanced sensitivity, enabling accurate discrimination and catalytic control at a modest energetic cost.
format Preprint
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institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Many Will Enter, Few Will Win: Cost and Sensitivity of Exploratory Dynamics
Koslover, Elena F
Lin, Milo M
Phillips, Rob
Biological Physics
A variety of biomolecular systems rely on exploratory dynamics to reach target locations or states within a cell. Without a mechanism to remotely sense and move directly towards a target, the system must sample over many paths, often including resetting transitions back to the origin. We investigate how exploratory dynamics can confer an important functional benefit: the ability to respond to small changes in parameters with large shifts in the steady-state behavior. However, such enhanced sensitivity comes at a cost: resetting cycles require energy dissipation in order to push the system out of its equilibrium steady state. We focus on minimalist models for two concrete examples: translational proofreading in the ribosome and microtubule length control via dynamic instability to illustrate the trade-offs between energetic cost and sensitivity. In the former, a driven hydrolysis step enhances the ability to distinguish between substrates and decoys with small binding energy differences. In the latter, resetting cycles enable catalytic control, with the steady-state length distribution modulated by sub-stoichiometric concentrations of a reusable catalyst. Synthesizing past models of these well-studied systems, we show how path-counting and circuit mapping approaches can be used to address fundamental questions such as the number of futile cycles inherent in translation and the steady-state length distribution of a dynamically unstable polymer. In both cases, a limited amount of thermodynamic driving is sufficient to yield a qualitative transition to a system with enhanced sensitivity, enabling accurate discrimination and catalytic control at a modest energetic cost.
title Many Will Enter, Few Will Win: Cost and Sensitivity of Exploratory Dynamics
topic Biological Physics
url https://arxiv.org/abs/2506.00775