Fraglingo: Molecular Design via Attachment-Aware Autoregressive Fragment Generation

Abstract

We introduce Fraglingo, an autoregressive molecular generator that constructs molecules step by step from chemically meaningful fragments connected through predefined attachment sites. At each generation step, Fraglingo jointly predicts which fragment to add and how it should attach by producing an attachment-aware fragment embedding and retrieving the nearest fragment through latent-space search. A wildcard-anchored readout represents both the growing molecule and candidate fragments relative to their attachment sites, enabling a single latent prediction to determine both fragment identity and attachment configuration. Because prediction operates in a continuous embedding space rather than over fixed fragment identifiers, larger fragment libraries can be introduced at inference time without retraining. This retrieval-based formulation provides a unified generation primitive for molecule generation, scaffold generation, scaffold decoration, and molecule optimization. Fraglingo also supports property-conditional generation, allowing desired molecular properties to guide the generation process. On controlled property-conditional benchmarks, Fraglingo achieves stronger joint property control than comparably trained baselines while maintaining competitive validity, uniqueness, and novelty. It also generalizes to fragment libraries up to four times larger than those used during training without retraining. Code is available at: https://anonymous.4open.science/r/FragLingo-3551.