用能量引导生成分子低能构象,仅需1-2步就高效找对结构。
Energy-Guided Generative Modeling for Low-Energy Molecular Structure Discovery
- 用流模型结合学习的能量场,边生成边往低能区引导。
- 在1-2步内生成高质量构象,且能按能量排序。
- 适合需要快速找稳定分子结构的研究者。
探索分子能量景观并识别基态构象是计算化学的核心挑战。传统基于物理的方法生成多样低能构象成本高;现有学习方法分散:生成模型捕捉构象多样性但能量校准不可靠,确定性预测器仅输出单一结构,无法体现集合变异性。本文提出EnFlow,据我们所知首个能量引导的生成框架,将基于流的构象生成与显式能量景观建模结合,实现构象集合与基态结构的联合生成。通过融合生成动力学与学习能量模型,EnFlow引导采样向构象景观的低能区域收敛,在极少数采样步数下提升结构保真度,并支持生成构象的能量排名。在GEOM-QM9和GEOM-Drugs数据集上的实验表明,EnFlow仅需1–2个ODE采样步骤即可在构象生成与基态识别上达到优秀表现。单点GFN2-xTB评估进一步显示,学习到的能量得分能保持生成构象间物理意义明确的能量排序。结果证明,显式建模能量景观是通过联合建模构象集合及其能量实现低能分子结构发现的有效策略。
原文摘要 · Abstract (English)
Exploring molecular energy landscapes and identifying ground-state conformations are central challenges in computational chemistry. However, generating diverse low-energy conformers from molecular graphs remains expensive with traditional physics-based pipelines. Existing learning-based approaches remain fragmented: generative models capture conformational diversity but often lack reliable energy calibration, whereas deterministic predictors focus on a single structure and fail to represent ensemble variability. Here we introduce EnFlow, to our knowledge, the first energy-guided generative framework that couples flow-based conformer generation with explicit energy landscape modeling for joint conformational ensemble generation and ground-state identification. By integrating generative dynamics with a learned energy model, EnFlow guides sampling toward low-energy regions of the conformational landscape, improving structural fidelity under extremely few sampling steps while enabling energy-based ranking of generated conformations. Experiments on GEOM-QM9 and GEOM-Drugs show that EnFlow achieves strong performance in conformer generation and ground-state identification while requiring only 1--2 ODE sampling steps. Single-point GFN2-xTB evaluations further show that the learned energy scores preserve physically meaningful energetic rankings of generated conformations. These results support explicit energy landscape modeling as an effective strategy for low-energy molecular structure discovery through joint modeling of conformational ensembles and their associated energies.
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