Alexei V. Tkachenko

Alexei V. Tkachenko, Bortolo Matteo Mognetti, Sergei Maslov

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.

Alexei V. Tkachenko

While Landauer's principle sets a fundamental energy limit for irreversible digital computation, we show that Deep Neural Networks (DNNs) implemented on analog physical substrates can operate under markedly different thermodynamic constraints. We distinguish between two classes of analog systems: dynamic and quasi-static. In dynamic systems, energy dissipation arises from neuron resets, with a lower bound governed by Landauer's principle. To analyse a quasi-static analog platform, we construct an explicit mapping of a generic feedforward DNN onto a physical system described by a model Hamiltonian. In this framework, inference can proceed reversibly, with no minimum free energy cost imposed by thermodynamics. We further analyze the training process in quasi-static analog networks and derive a fundamental lower bound on its energy cost, rooted in the interplay between thermal and statistical noise. Our results suggest that while analog implementations can outperform digital ones during inference, the thermodynamic cost of training scales similarly in both paradigms.