通过匹配分子力场的曲率信息,提升粗粒度模拟精度与泛化能力。
Hessian Matching for Machine-Learned Coarse-Grained Molecular Dynamics

- 用随机向量估计海森矩阵乘积,无需计算完整海森矩阵。
- 在9个蛋白上8个表现优于传统方法,最大熵差异降低85%。
- 适合需要高精度和强泛化的生物分子模拟研究者。
粗粒度(CG)分子动力学可实现对生物分子等原子系统的长时间尺度模拟,但现有基于力匹配训练的神经势能仅捕捉自由能面的梯度,忽略其曲率。本文提出一种新框架,在力匹配基础上引入随机海森-向量乘积(HVP)匹配,将二阶曲率信息融入CG势能,而无需构建完整海森矩阵。我们推导出目标CG海森矩阵的分解:模型无关的投影原子级海森矩阵(预先计算一次),以及在线低开销计算的模型相关协方差修正项。通过使用随机探针向量,构造无偏的随机海森匹配目标估计器。我们在9个未参与训练的快速折叠蛋白基准上评估该方法,发现HVP匹配在8个蛋白上的慢模式指标优于纯力匹配,最大蛋白的最慢集体模态上,CG与参考分布间的Kullback--Leibler散度降低达85%。结果表明,高阶物理监督是实现更精确、更具迁移性的生物分子粗粒度势能的有效路径。
原文摘要 · Abstract (English)
Coarse-grained (CG) molecular dynamics enables simulations of atomic systems such as biomolecules at timescales inaccessible to all-atom (AA) methods, but existing CG neural potentials trained via force matching capture only the gradient of the free-energy surface, leaving its curvature unconstrained. We introduce a framework that augments force matching with stochastic Hessian-vector product (HVP) matching, instilling second-order curvature information into CG potentials without constructing the full Hessian. We derive a decomposition of the target CG Hessian into a model-independent projected AA Hessian, precomputed once before training, and a model-dependent covariance correction computed online at negligible cost. We construct an unbiased stochastic estimator of the Hessian-matching objective by using random probe vectors. We evaluate our method by comparing against force matching on a benchmark of nine fast-folding proteins unseen during training. HVP matching outperforms plain force matching on 8 of 9 proteins on slow-mode metrics, with reductions of up to 85% in the Kullback--Leibler divergence between the CG and reference distributions along the slowest collective mode of the largest protein. Our results demonstrate that higher-order physical supervision is a practical path to more accurate and transferable CG potentials for biomolecular simulation.
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