Fast Organic Crystal Structure Prediction with Unit Cell Flow Matching

Organic crystal structure prediction (CSP) is a requirement for computational modelling of organic solids. Traditional CSP is accurate but relies on exhaustive search, costing several CPU-years per molecule. Generative models such as OXtal dramatically reduce this cost by sampling stable organic crystal structures directly. However, OXtal forgoes explicit lattice parametrization in favour of modelling large crops of the bulk material with expensive triangle layers, which can incur a computational cost of minutes per molecule. In this paper, we reduce this to seconds with Clari, a large-scale flow matching model that generates redundancy-free unit cells and replaces triangle layers with pure pair-bias attention. Clari requires only atom types and bonds as input and does not need an RDKit-sanitizable input molecule, which expands its applicability to challenging chemistries such as fullerenes, metal complexes, and atom clusters. We further ablate key design choices such as auxiliary losses, timestep distributions, noise priors, and self-conditioning. Because Clari also models explicit hydrogens, it supports inference-time scaling via direct energy ranking, without any decoration or relaxation step. On OXtal's aggregated test set, we generate 1000 crystals and select the best 30 ranked by energy, surpassing OXtal's solve rate while obtaining a speedup of $5$-$8\times$. We also introduce a new test split of diverse and complex molecules for future benchmarking. Our contributions enable CSP within seconds, making large-scale virtual screening of organic solids practical.