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bioRxiv · 10.1101/2025.08.12.669871

NetMD: Unsupervised Synchronization of Molecular Dynamics Trajectories via Graph Embedding and Time Warping

Mangoni, M.·Bianco, S. D.·Petrizzelli, F.·Pieroni, M.·Guzzi, P. H.·Caputo, V.·Biagini, T.·Mazza, T.
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Abstract

Molecular dynamics (MD) simulations yield detailed atomistic views of biomolecular processes, yet comparing independent trajectories is hindered by stochastic divergence. Here, we introduce NetMD, a computational approach that synchronizes and analyzes MD trajectories by combining graph-based representations with dynamic time warping. Frames are transformed into residue-contact graphs, entropy-filtered to retain variable interactions, and embedded as low-dimensional vectors. NetMD then uses time-warping barycenter averaging to align these vector trajectories, yielding a consensus "average" trajectory while pruning the outlier simulations. Applied to diverse systems, such as transporters, demethylases, and protein complexes, NetMD revealed shared multiphase dynamics and pinpointed mutation- or ligand-specific deviations. Thus, this method enables an unsupervised, time-resolved comparison of MD ensembles across conditions. It is robust, broadly applicable, and available as an open-source software, offering a powerful tool for uncovering common patterns and critical divergences in biomolecular dynamics.

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Mangoni, M., Bianco, S. D., Petrizzelli, F., Pieroni, M., Guzzi, P. H., Caputo, V., Biagini, T., Mazza, T.. 2025-08-15. NetMD: Unsupervised Synchronization of Molecular Dynamics Trajectories via Graph Embedding and Time Warping. https://doi.org/10.1101/2025.08.12.669871

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