Many will enter, few will win: Cost and sensitivity of exploratory dynamics
Year: 2025
Type: article
Abstract: 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 toward 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 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 substoichiometric 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.
Source: Biophysical Journal
Authors: Elena F. Koslover, Milo M. Lin, Rob Phillips
Language: English
Subfield: Statistical and Nonlinear Physics
Field: Physics and Astronomy
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Awards: Research - University of Texas, Southwestern Medical Center at Dallas (2024), Physical Genomics: From Single-Cell to Evolutionary Dynamics, Collaborative Research: Integrating Theory and Experiment to Unravel Protein Transport in the ER, G9000021315, G9000136331, G9000155680, G9000158519, G9000181547, Discovering interpretable mechanisms explaining high dimensional biomolecular data, Mapping epistatic interactions in molecular evolution of antibiotic resistance
OpenAlex ID: W4414035736