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Updated: Sep 13, 2025

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
An information ratchet improves selectivity in molecular recognition under non-equilibrium conditions
Benjamin M W Roberts1, Erica Del Grosso2, Emanuele Penocchio3
1Department of Chemical Sciences, University of Padua, Padua, Italy.
None:
Molecular recognition is essential for controlling chemical processes, passing molecular instructions to elicit responses including structure formation, signalling and replication. Usually, the selectivity of molecular recognition is under thermodynamic control; however, when a higher fidelity is required, nature improves recognition selectivity by an error correction mechanism under an energy-dissipating kinetic-control regime. Here, exploiting DNA hybridization as a model, we present an abiotic example of an information ratchet mechanism that increases selectivity for the 'correct' duplex from 2:1 at equilibrium to 6:1 under energy-dissipating conditions. Structural asymmetry in the DNA strands introduces kinetic asymmetry in the reaction network, enabling enrichment under non-equilibrium conditions. We quantify the free-energy cost associated with enhanced selectivity using Shannon entropy formalism, finding that an increase in information of 0.33 bits is associated with at least 3.0 kJ mol-1 of free energy. Moreover, the minimalistic structures of our error reduction system demonstrates that biomachinery is not necessary to increase molecular recognition fidelities above the thermodynamically expected values, thereby pointing a way towards solving Eigen's paradox.
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