3D-Fit finds LLMs can handle multiple molecular constraints, but still lag diffusion models
insilicomedicine · hf · 2026-07-21
A new benchmark tests whether LLMs can handle 3D molecular constraints
This paper studies whether general-purpose LLMs can reason about 3D spatial constraints in structure-based drug design, compared with specialized diffusion models.
- The task is 3D ligand generation conditioned on protein pockets and additional constraints such as:
- anchor fragments
- pharmacophore points
- mandatory pocket-ligand interactions
- The authors introduce 3D-Fit, a token-efficient benchmark for evaluating multi-conditioned spatial molecule generation.
- Results show a clear gap: LLMs still lag behind state-of-the-art diffusion models, but they can already handle multiple spatial constraints simultaneously and may scale well to heterogeneous setups.
The work helps clarify where LLMs are still weak in molecular design and where they may become useful.
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