Chain-of-Generation: Progressive Latent Diffusion for Text-Guided Molecular Design

ICLR 2026 Conference Submission21026 Authors

Keywords: Drug Discovery, Generative Model, Chain of thought, Planning Strategy

Abstract:

Text-conditioned molecular generation aims to translate natural-language descriptions into chemical structures, enabling scientists to specify functional groups, scaffolds, and physicochemical constraints without handcrafted rules.
Diffusion-based models, particularly latent diffusion models (LDMs), have recently shown promise by performing stochastic search in a continuous latent space that compactly captures molecular semantics.
Yet existing methods rely on one-shot conditioning, where the entire prompt is encoded once and applied throughout diffusion, making it hard to satisfy all the requirements in the prompt.
We discuss three outstanding challenges of one-shot conditioning generation, including the poor interpretability of the generated components, the failure to generate all substructures, and the ambiguity in considering all requirements simultaneously.
We then propose three principles to address those challenges, motivated by which we propose Chain-of-Generation (CoG), a training-free multi-stage latent diffusion framework.
CoG decomposes each prompt into curriculum-ordered semantic segments and progressively incorporates them as intermediate goals, guiding the denoising trajectory toward molecules that satisfy increasingly rich linguistic constraints.
To reinforce semantic guidance, we further introduce a post-alignment learning phase that strengthens the correspondence between textual and molecular latent spaces.
Extensive experiments on benchmark and real-world tasks demonstrate that CoG yields higher semantic alignment, diversity, and controllability than one-shot baselines, producing molecules that more faithfully reflect complex, compositional prompts while offering transparent insight into the generation process.

Primary Area: applications to physical sciences (physics, chemistry, biology, etc.)

Submission Number: 21026