arXiv:2508.14748cs.LGcs.AI2025-08被引 1

让分子生成模型同时满足结构和性质双重约束,无需重新训练。

Cross-Modality Controlled Molecule Generation with Diffusion Language Model

  • 用两个可训练模块分别控制分子结构和化学性质
  • 分两阶段生成:先固定骨架,再优化性质
  • 支持新增约束,适合药物设计快速迭代

现有的基于SMILES的分子生成扩散模型通常只支持单一模态约束,需在训练初期注入条件信号,并在约束变化时从头重新训练。然而真实场景常涉及跨模态多约束,且研究过程中可能不断出现新约束。为此,本文提出跨模态可控分子生成框架CMCM-DLM,基于预训练扩散模型,引入结构控制模块(SCM)和性质控制模块(PCM),分两阶段生成:第一阶段通过SCM在早期扩散步骤中注入结构约束,锚定分子骨架;第二阶段利用PCM在后期推理中引导生成,使分子化学性质匹配目标。在多个数据集上的实验表明,该方法高效且具备良好适应性,显著推进了药物发现中的分子生成能力。

原文摘要 · Abstract (English)

Current SMILES-based diffusion models for molecule generation typically support only unimodal constraint. They inject conditioning signals at the start of the training process and require retraining a new model from scratch whenever the constraint changes. However, real-world applications often involve multiple constraints across different modalities, and additional constraints may emerge over the course of a study. This raises a challenge: how to extend a pre-trained diffusion model not only to support cross-modality constraints but also to incorporate new ones without retraining. To tackle this problem, we propose the Cross-Modality Controlled Molecule Generation with Diffusion Language Model (CMCM-DLM), demonstrated by two distinct cross modalities: molecular structure and chemical properties. Our approach builds upon a pre-trained diffusion model, incorporating two trainable modules, the Structure Control Module (SCM) and the Property Control Module (PCM), and operates in two distinct phases during the generation process. In Phase I, we employs the SCM to inject structural constraints during the early diffusion steps, effectively anchoring the molecular backbone. Phase II builds on this by further introducing PCM to guide the later stages of inference to refine the generated molecules, ensuring their chemical properties match the specified targets. Experimental results on multiple datasets demonstrate the efficiency and adaptability of our approach, highlighting CMCM-DLM's significant advancement in molecular generation for drug discovery applications.

分子生成扩散模型多模态

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