Split-Flows: Measure Transport and Information Loss Across Molecular Resolutions

Sander Hummerich, Ullrich Koethe, Tristan Bereau

TL;DR: Split-flows is a new flow-based method that treats backmapping as continuous measure transport, enabling accurate conditional sampling, and the first tractable computation of mapping entropy in coarse-grained molecular models.

Abstract: By reducing resolution, coarse-grained models greatly accelerate molecular simulations, unlocking access to long-timescale phenomena, though at the expense of microscopic information. Recovering this fine-grained detail is essential for tasks that depend on atomistic accuracy, making backmapping a central challenge in molecular modeling. We introduce split-flows, a novel flow-based approach that reinterprets backmapping as a continuous-time measure transport across resolutions. Unlike existing generative strategies, split-flows establish a direct probabilistic link between resolutions, enabling expressive conditional sampling of atomistic structures and—for the first time—a tractable route to computing mapping entropies, an information-theoretic measure of the irreducible detail lost in coarse-graining. We demonstrate these capabilities on diverse molecular systems, including Chignolin, a lipid bilayer, and alanine dipeptide, highlighting split-flows as a principled framework for accurate backmapping and systematic evaluation of coarse-grained models.

Submission Number: 738