LLM 在空间约束下的分子生成能力:3D-Fit 基准测试揭示潜力与差距

HuggingFace Daily Papers(社区热门论文)·2026-07-20 08:00·46天前
AI 导读

一项新研究系统评估了通用 LLM 在结构药物设计(SBDD)中处理复杂 3D 空间约束的能力。研究者引入 3D-Fit 基准测试策略,对比 LLM 与专用扩散模型在蛋白口袋、锚定片段、药效团点及强制口袋-配体相互作用等多条件分子生成任务上的表现。结果显示,LLM 虽仍落后于 SOTA 方法,但已能同时处理多种空间约束,具备向异构场景扩展的潜力。

HuggingFace Daily Papers(社区热门论文)
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LLM 在空间约束下的分子生成能力:3D-Fit 基准测试揭示潜力与差距

2026-07-20 08:00· 46天前
AI 导读

一项新研究系统评估了通用 LLM 在结构药物设计(SBDD)中处理复杂 3D 空间约束的能力。研究者引入 3D-Fit 基准测试策略,对比 LLM 与专用扩散模型在蛋白口袋、锚定片段、药效团点及强制口袋-配体相互作用等多条件分子生成任务上的表现。结果显示,LLM 虽仍落后于 SOTA 方法,但已能同时处理多种空间约束,具备向异构场景扩展的潜力。

Structure-based drug design (SBDD) leverages the 3D structure of protein targets, often complemented by other spatial constraints, to generate candidate binding molecules. While diffusion models have dominated as a leading paradigm for high-quality 3D molecule generation, LLM-based methods are rapidly emerging in molecular design and have shown competitive performance in pocket-conditioned molecular generation. However, their ability to reason about physics and 3D spatial environments is largely underexplored. In this work, we systematically analyze whether current general-purpose LLMs are capable of navigating complex 3D constraints compared to established baselines such as specialized diffusion models. We consider 3D ligand generation conditioned on protein pockets together with ligand- and interaction-derived spatial constraints, including anchor fragments, pharmacophore points, and mandatory pocket-ligand interactions. To enable this evaluation, we introduce 3D-Fit - a token-efficient benchmarking strategy for assessing LLM performance on multi-conditioned spatial molecule generation. Our findings reveal a clear pattern in LLM spatial capabilities: while they still lag behind state-of-the-art approaches, they are promising and can handle multiple spatial constraints simultaneously, enabling scaling to heterogeneous setups.

来源:HuggingFace Daily Papers(社区热门论文)· arxiv.org