提升分子生成的几何表示质量,让模型生成更高效准确的分子结构。
Toward Better Geometric Representations for Molecule Generative Models

- 设计多层级表示头与对齐损失,优化预训练编码器的使用效果。
- 在GEOM-DRUG数据集上达到97.28%有效性与98.51%稳定性,显著领先。
- 适合分子生成、药物设计等需高精度结构建模的研究者使用。
几何表示条件下的分子生成通过将分子表示学习与结构生成解耦,显著提升了生成效率与质量。然而其性能受限于表示空间的质量:如UniMol等预训练编码器产生的表示存在非平滑、未充分使用等问题。本文提出LENSEs框架,引入三项互补机制:(1) 在生成任务中联合训练的表示头,提取多层级特征;(2) 基于语义信息的分子感知损失,优化生成器在语义表示空间中的表现;(3) 节点级表示对齐(REPA)损失,显式对齐生成器隐藏状态与编码器表示,缩小预训练与生成间的语义鸿沟。在挑战性数据集GEOM-DRUG上,LENSEs实现97.28%有效性与98.51%分子稳定性,超越现有先进方法。进一步通过利普希茨常数降低4.6倍及QM9探针任务分析,验证了表示更平滑、更具信息量。结果表明,带对齐目标的生成训练可成为分子编码器的新预训练范式。
原文摘要 · Abstract (English)
Geometric representation-conditioned molecule generation provides an effective paradigm that decouples molecule representation modeling from structure generation. By decoupling molecule generation into two stages-first generating a meaningful molecule representation, and then generating a 3D molecule conditioned on this representation-the efficiency and quality of the generation process can be significantly enhanced. However, its effectiveness is fundamentally limited by the quality of the representation space: pretrained molecular encoders, such as UniMol, produce representations that are non-smooth and not fully exploited during the generative training process. In this work, we propose LENSEs, a framework that better exploits the potential of molecule representations in representation-conditioned generation methods. In particular, LENSEs introduces three complementary mechanisms: (1) a representation head, simultaneously trained during generative tasks, that extracts multi-level representations from the pretrained encoder; (2) a molecule perceptual loss that optimizes the generator in a semantic-informative representation space; and (3) a node-level representation alignment (REPA) loss that explicitly aligns the generator's hidden states with encoder representations, reducing the semantic gap between pretraining and generation. We demonstrate the effectiveness of these improvements through extensive molecule generation tasks. Specifically, on the challenging molecule generation dataset GEOM-DRUG, LENSEs achieves 97.28% validity and 98.51% molecule stability, surpassing existing advanced methods. Further analyses through Lipschitz constant reduction (4.6x) and QM9 probing tasks also demonstrate the smoother, more informative refined representations, establishing generative training with alignment objectives as a potential pretraining paradigm for molecular encoders.
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