融合分子序列、结构与构象的多模态模型,提升性质预测精度。
MolFM-Lite: Multi-Modal Molecular Property Prediction with Conformer Ensemble Attention and Cross-Modal Fusion
- 用构象集合注意力和跨模态融合,同时处理一维序列、二维图与三维构象。
- 三模态融合相比单模态提升7-11% AUC,构象集合比单构象高约2%。
- 适合需考虑分子动态结构的药物设计与性质预测研究者使用。
现有分子性质预测模型通常依赖单一分子表示(序列、图或3D结构),并将分子几何视为静态。本文提出MolFM-Lite,一种多模态模型,通过交叉注意力融合自我编码序列(SELFIES,1D)、分子图(2D)和构象集合(3D)信息,并利用特征线性调制(FiLM)引入实验上下文条件。主要方法贡献包括:(1) 构象集合注意力机制,结合可学习注意力与基于RDKit生成构象的玻尔兹曼加权先验,捕捉分子构型的热力学分布;(2) 跨模态融合层,各模态可相互关注,实现互补信息共享。在四个MoleculeNet骨架划分基准上评估,采用自建数据集划分并重新评估所有基线。全面消融实验表明各组件独立贡献,三模态融合相比单模态基线提升7-11% AUC,构象集合相较单构象版本提升约2%。在约25万分子的ZINC250K上进行预训练,通过跨模态对比与掩码原子目标,以较低算力成本实现有效权重初始化。代码、模型与数据划分均已开源,支持可复现性。
原文摘要 · Abstract (English)
Most machine learning models for molecular property prediction rely on a single molecular representation (either a sequence, a graph, or a 3D structure) and treat molecular geometry as static. We present MolFM-Lite, a multi-modal model that jointly encodes SELFIES sequences (1D), molecular graphs (2D), and conformer ensembles (3D) through cross-attention fusion, while conditioning predictions on experimental context via Feature-wise Linear Modulation (FiLM). Our main methodological contributions are: (1) a conformer ensemble attention mechanism that combines learnable attention with Boltzmann-weighted priors over multiple RDKit-generated conformers, capturing the thermodynamic distribution of molecular shapes; and (2) a cross-modal fusion layer where each modality can attend to others, enabling complementary information sharing. We evaluate on four MoleculeNet scaffold-split benchmarks using our model's own splits, and report all baselines re-evaluated under the same protocol. Comprehensive ablation studies across all four datasets confirm that each architectural component contributes independently, with tri-modal fusion providing 7-11% AUC improvement over single-modality baselines and conformer ensembles adding approximately 2% over single-conformer variants. Pre-training on ZINC250K (~250K molecules) using cross-modal contrastive and masked-atom objectives enables effective weight initialization at modest compute cost. We release all code, trained models, and data splits to support reproducibility.
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