提出可控制分子生成模型CoMole,实现高效精准的分子设计。
Controllable Molecular Generative Foundation Models

- 基于基元感知的图扩散框架,统一处理多种分子设计任务。
- 在9个目标上可控性排名第一,平均误差降低48.2%,有效性超0.94。
- 仅微调任务嵌入即可迁移控制能力,适合药物与材料研发人员。
尽管基础模型在语言和视觉领域取得成功,但分子图生成仍缺乏统一的异构设计框架,且可控性不可靠。强化学习(RL)虽为任务优化提供自然后训练机制,但受限于原子级动作空间过大及化学无效中间状态。本文提出可控分子生成基础模型CoMole,采用统一的基元感知图扩散流程。通过学习基元感知的图空间,将预训练结构先验转化为可控生成,利用RL在化学意义明确的决策上优化条件反向策略。理论分析了原子级RL的瓶颈,并验证基元感知策略优化的有效性。在涵盖材料与药物发现的三个异构基准上,CoMole在全部九个目标上排名第一,相对最强基线降低48.2%的平均绝对误差(MAE),且无需规则修正或后期过滤,有效性保持在0.94以上。进一步表明,仅通过微调任务嵌入即可将可控性迁移至未见属性,性能媲美强任务专用模型。
原文摘要 · Abstract (English)
Despite the success of foundation models in language and vision, molecular graph generation still lacks a unified framework for heterogeneous design tasks with reliable controllability. While reinforcement learning (RL) offers a natural post-training mechanism for task-specific optimization, applying it to graph generative models is hindered by the vast atom-wise action spaces and chemically invalid intermediate states. We propose \textbf{Co}ntrollable \textbf{Mole}cular Generative Foundation Models (CoMole), built with a unified motif-aware graph diffusion pipeline. By learning a motif-aware graph space, CoMole transfers pretrained structural priors into controllable generation, where RL optimizes conditional reverse policies over chemically meaningful decisions. We theoretically characterize the bottleneck of atom-level RL and justify motif-aware policy optimization. Across three heterogeneous benchmarks spanning materials and drug discovery, CoMole ranks first in controllability on all nine targets, reduces MAE by up to 48.2% relative to the strongest baselines, and maintains validity above 0.94 without rule-based correction or post-hoc filtering. We further show that CoMole transfers controllability to unseen properties by optimizing only task embeddings with the generator frozen, achieving performance competitive with strong task-specific baselines.
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