用确定性流匹配替代随机扩散模型,高效生成反应路径与过渡态。
Flow matching for reaction pathway generation
- 采用确定性流匹配构建分子生成路径,提升可控性与效率。
- 在基准测试中实现亚秒级采样,过渡态几何精度与能垒预测更优。
- 适合需要高精度、低计算成本的化学反应路径生成任务。
揭示反应机理依赖于高效生成过渡态(TS)、产物及完整反应网络。近期生成模型如基于扩散的过渡态采样和序列模型的产物生成,提供了比量子化学搜索更快的替代方案。但扩散模型受限于其随机微分方程(SDE)动力学,存在效率低、控制性差的问题。本文表明,确定性的流匹配(ODE形式)可取代基于SDE的扩散模型用于分子与反应生成。我们提出MolGEN,一种条件流匹配框架,学习最优传输路径将高斯先验映射到目标化学分布。在TSDiff和OA-ReactDiff使用的基准上,MolGEN在过渡态几何精度和能垒预测方面超越现有方法,采样时间缩短至亚秒级。同时支持开放式产物生成,达到竞争性top-k准确率,并避免序列模型常见的质量/电子守恒违规。在γ-酮氢过氧化物分解网络的真实测试中,相比字符串基基线,MolGEN以更少的量子化学计算获得更高比例的有效且意图明确的过渡态。结果表明,确定性流匹配为分子生成提供了统一、准确且计算高效的基石,预示其将成为未来分子生成的核心范式。
原文摘要 · Abstract (English)
Elucidating reaction mechanisms hinges on efficiently generating transition states (TSs), products, and complete reaction networks. Recent generative models, such as diffusion models for TS sampling and sequence-based architectures for product generation, offer faster alternatives to quantum-chemistry searches. But diffusion models remain constrained by their stochastic differential equation (SDE) dynamics, which suffer from inefficiency and limited controllability. We show that flow matching, a deterministic ordinary differential (ODE) formulation, can replace SDE-based diffusion for molecular and reaction generation. We introduce MolGEN, a conditional flow-matching framework that learns an optimal transport path to transport Gaussian priors to target chemical distributions. On benchmarks used by TSDiff and OA-ReactDiff, MolGEN surpasses TS geometry accuracy and barrier-height prediction while reducing sampling to sub-second inference. MolGEN also supports open-ended product generation with competitive top-k accuracy and avoids mass/electron-balance violations common to sequence models. In a realistic test on the $γ$-ketohydroperoxide decomposition network, MolGEN yields higher fractions of valid and intended TSs with markedly fewer quantum-chemistry evaluations than string-based baselines. These results demonstrate that deterministic flow matching provides a unified, accurate, and computationally efficient foundation for molecular generative modeling, signaling that flow matching is the future for molecular generation across chemistry.
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