提出时空耦合机制，提升多模态生物分子协同设计的一致性与有效性。
Demystifying Multimodal Biomolecular Co-design With Intrinsic Geodesic Coupling
- 通过优化异构模态间的时序耦合关系，实现更自然的生成过程
- 在药物设计和蛋白质设计任务中均优于同步与随机耦合基线
- 适合关注生物分子生成质量与多样性的研究者使用
蛋白质和小分子配体等生物分子在生物系统中起核心作用，源于序列与三维结构之间的紧密互动。近期的生物分子协同生成模型试图通过联合建模相关模态来捕捉这种互动，但现有方法大多采用独立并行的边缘生成过程，隐式施加固定的同步耦合。我们指出，训练与生成过程中各边缘过程的时序耦合方式是一个被忽视的关键自由度，不当耦合会导致高方差监督和不一致的中间状态，影响模态一致性。为此，我们提出GeoCoupling框架，系统优化异构模态间的时序耦合。在基于结构的药物设计和无条件蛋白质设计任务上的实验证明，所学耦合始终优于同步和随机耦合基线，生成的生物分子具有更高的物理合理性和多样性。
原文摘要 · Abstract (English)
Biomolecules such as proteins and small-molecule ligands play a central role in biological systems, arising from the tight interplay between sequence and three-dimensional structure. Recent generative models for biomolecular co-design aim to capture this interplay by jointly modeling coupled modalities. However, existing approaches largely adopt a parallel execution of marginal generative processes, implicitly enforcing fixed synchronous coupling. We argue that a critical but overlooked degree of freedom lies in how these marginal processes are temporally coupled during training and generation, where inappropriate coupling can introduce high-variance supervision and inconsistent intermediate states, affecting modality consistency. To address this, we introduce GeoCoupling, a systematic framework that optimizes for temporal couplings between heterogeneous modalities. Empirical results across structure-based drug design and unconditional protein design demonstrate the learned couplings consistently outperform synchronous and randomly coupled baselines, yielding biomolecules with improved physical validity and diversity.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品；中文卡片由大模型生成，请以原文为准。