Hessian Matching for Machine-Learned Coarse-Grained Molecular Dynamics

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.

Holographic generative flows with AdS/CFT

We present a framework for generative machine learning that leverages the holographic principle of quantum gravity, or to be more precise its manifestation as the anti-de Sitter/conformal field theory (AdS/CFT) correspondence, with techniques for deep learning and transport theory. Our proposal is to represent the flow of data from a base distribution to some learned distribution using the bulk-to-boundary mapping of scalar fields in AdS. In the language of machine learning, we are representing and augmenting the flow-matching algorithm with AdS physics. Using a checkerboard toy dataset and MNIST, we find that our model achieves faster and higher quality convergence than comparable physics-free flow-matching models. Our method provides a physically interpretable version of flow matching. More broadly, it establishes the utility of AdS physics and geometry in the development of novel paradigms in generative modeling.