Evolutionary chemical learning in dimerization networks

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Main Authors: Tkachenko, Alexei V., Mognetti, Bortolo Matteo, Maslov, Sergei
Format: Preprint
Published: 2025
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author Tkachenko, Alexei V.
Mognetti, Bortolo Matteo
Maslov, Sergei
author_facet Tkachenko, Alexei V.
Mognetti, Bortolo Matteo
Maslov, Sergei
contents We present a novel framework for chemical learning based on Competitive Dimerization Networks (CDNs) - systems in which multiple molecular species, e.g. proteins or DNA/RNA oligomers, reversibly bind to form dimers. We show that these networks can be trained in vitro through directed evolution, enabling the implementation of complex learning tasks such as multiclass classification without digital hardware or explicit parameter tuning. Each molecular species functions analogously to a neuron, with binding affinities acting as tunable synaptic weights. A training protocol involving mutation, selection, and amplification of DNA-based components allows CDNs to robustly discriminate among noisy input patterns. The resulting classifiers exhibit strong output contrast and high mutual information between input and output, especially when guided by a contrast-enhancing loss function. Comparative analysis with in silico gradient descent training reveals closely correlated performance. These results establish CDNs as a promising platform for analog physical computation, bridging synthetic biology and machine learning, and advancing the development of adaptive, energy-efficient molecular computing systems.
format Preprint
id arxiv_https___arxiv_org_abs_2506_14006
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Evolutionary chemical learning in dimerization networks
Tkachenko, Alexei V.
Mognetti, Bortolo Matteo
Maslov, Sergei
Statistical Mechanics
Disordered Systems and Neural Networks
Machine Learning
Adaptation and Self-Organizing Systems
Data Analysis, Statistics and Probability
Molecular Networks
We present a novel framework for chemical learning based on Competitive Dimerization Networks (CDNs) - systems in which multiple molecular species, e.g. proteins or DNA/RNA oligomers, reversibly bind to form dimers. We show that these networks can be trained in vitro through directed evolution, enabling the implementation of complex learning tasks such as multiclass classification without digital hardware or explicit parameter tuning. Each molecular species functions analogously to a neuron, with binding affinities acting as tunable synaptic weights. A training protocol involving mutation, selection, and amplification of DNA-based components allows CDNs to robustly discriminate among noisy input patterns. The resulting classifiers exhibit strong output contrast and high mutual information between input and output, especially when guided by a contrast-enhancing loss function. Comparative analysis with in silico gradient descent training reveals closely correlated performance. These results establish CDNs as a promising platform for analog physical computation, bridging synthetic biology and machine learning, and advancing the development of adaptive, energy-efficient molecular computing systems.
title Evolutionary chemical learning in dimerization networks
topic Statistical Mechanics
Disordered Systems and Neural Networks
Machine Learning
Adaptation and Self-Organizing Systems
Data Analysis, Statistics and Probability
Molecular Networks
url https://arxiv.org/abs/2506.14006