q-bio.BMSep 28, 2026

Where Should Physics Enter a Molecular Crystal Generator?

Authors: Haocheng Tang, Junmei Wang, Wengong Jin

Organizations: Khoury College of Computer Science Northeastern University Boston, MA 02115, USA · School of Pharmacy University of Pittsburgh Pittsburgh, PA 15213, USA

Abstract

Generative models make molecular crystal structure prediction fast, but their samples still exhibit geometric and packing violations. Physics can be introduced during training, post-training, or inference, yet these choices are rarely compared with the generator and physical signal held fixed. We introduce CrystAF, an all-atom crystal flow-map generation model, and use it with the UMA interatomic potential to systematically study where physics should enter. Post-training learns physical preferences directly into CrystAF, improving molecular validity and crystal packing while leaving sampling unchanged: physics is paid for once during training rather than repeatedly at deployment. In contrast, UMA relaxation is effective at repairing local clashes but makes generation 6--26×\times slower, while learning from relaxed targets provides little benefit. These routes are complementary rather than competing. Physics-informed post-training first shifts the generated distribution toward more physically reasonable structures, after which inexpensive inference-time corrections further remove clashes and restore stereochemistry that the generator cannot represent. Importantly, the same post-training strategy also improves the multi-step all-atom Clari-M and rigid-body MolCrystalFlow generators, demonstrating transfer across architectures and representations. Together, our results suggest a simple principle: learn reusable physical alignment into the generator, and reserve inference-time physics for residual constraints that are better corrected than learned.

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