arXiv:2605.18381cs.LG2026-05

用能量模型生成符合物理规律的分子,性能领先且可控制。

Generating Physically Consistent Molecules with Energy-Based Models

论文配图:Generating Physically Consistent Molecules with Energy-Based Models
图 1 · 摘自论文原文
  • 基于能量场学习原子加性势能,无需训练时模拟
  • 在QM9和GEOM-Drugs上达到当前最佳性能
  • 可直接用于分子质量评估与零样本链接设计

平衡态分子遵循玻尔兹曼分布,因此能量景观是物理上合理的建模目标。然而,从数据中学习该景观困难,且学习后难以采样。扩散与流匹配模型通过学习噪声到数据的时间条件梯度或传输场绕过这些问题,但牺牲了能量先验。我们提出EBMol,一种能量基模型(EBM),通过学习无显式模拟的原子加性标量势能恢复这一先验。方法采用受流启发的还原场匹配目标以逼近能量景观。采样使用镜像朗之万算法,统一更新原子位置与类型,并引入并行退火实现推理时计算扩展。EBMol是首个在3D分子生成上于QM9和GEOM-Drugs达到顶尖性能的能量基模型。此外,我们证明学习到的能量景观可作为分子构型排序与过滤的严谨质量指标,并展示通过势能组合实现形状引导采样及零样本连接子设计,无需重新训练。

原文摘要 · Abstract (English)

Molecules in equilibrium follow a Boltzmann distribution, making the underlying energy landscape a physically grounded modeling objective. However, such landscapes are difficult to learn from data and, once learned, hard to sample from. Diffusion and flow-matching models sidestep these difficulties by learning a time-conditional score or transport field between noise and data, losing the energy inductive bias in exchange for a more tractable training objective. We introduce EBMol, an energy-based model (EBM) that restores this inductive bias by learning an atom-additive scalar potential without explicit simulation during training. Our method employs a flow-inspired Restoring Field Matching objective to approximate the energy landscape. We adopt the Mirror-Langevin algorithm for sampling, enabling unified updates of atomic positions and types, and incorporate parallel tempering for inference-time compute scaling. EBMol is the first EBM for 3D molecular generation to achieve state-of-the-art performance on QM9 and GEOM-Drugs. Moreover, we show that the learned energy landscape serves as a principled quality metric for ranking and filtering configurations, and demonstrate controllable generation without retraining through shape-steered sampling via potential composition and zero-shot linker design.

分子生成能量模型物理先验可控生成

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