Machine learning kinetics from molecular dynamics data

Studying the dynamical behavior of a system often depends on characterizing how it transitions between long-lived states. Because such transitions are rare, observing them usually requires specialized enhanced sampling techniques. Transition Path Sampling (TPS) is a well-established method for generating reactive trajectories, which is simple to implement and does not require the definition of a preconceived reaction coordinate. However, its efficiency is limited by its sequential nature and the resulting correlations between sampled paths. Previous work addressed this limitation by combining TPS with a sampling scheme based on conditioned Boltzmann Generators, a generative machine learning model capable of sampling a given target probability distribution. This approach produces uncorrelated transition paths but relies on an accurate reaction coordinate, which is rarely known in advance. Building on recent advances in committor learning, specifically on the Artificial Intelligence for Molecular Mechanism Discovery (AIMMD) method, in this work we introduce GenAIMMD, an iterative algorithm that actively and self-consistently learns the ideal reaction coordinate (the committor) and trains a conditioned Boltzmann Generator to sample from arbitrary bias windows along it. GenAIMMD thereby provides a correlation-free and fully parallelizable path sampling scheme that does not require prior knowledge of the system's transition mechanism. We apply GenAIMMD to a two-dimensional toy model and a higher-dimensional polymer system. In both cases, GenAIMMD succeeds in training the Boltzmann Generator and learning the committor. Benchmark results show a substantial increase in performance compared to standard TPS.

Machine learning interatomic potentials (MLIPs) enable efficient and accurate atomistic simulations but depend critically on the quality and diversity of the training data. We introduce Stein kernelized molecular dynamics (SKMD), an enhanced sampling method that uses interacting particle dynamics to acquire informative training configurations for the active learning and fine-tuning of MLIPs. SKMD corresponds to a stochastic variant of Stein variational gradient descent that is adapted for molecular dynamics by incorporating asynchronous particle updates and a kernel of global atomic descriptors, which provides a symmetry-aware measure of configurational similarity. Unlike other enhanced samplers used in molecular dynamics, SKMD preserves the Boltzmann distribution as the asymptotic distribution of the dynamics. This property enforces a balance between the exploration of diverse configurations and attraction toward high-probability regions of the energy landscape. We further propose an approach to efficient online data acquisition using an adaptive stopping criterion that selects non-redundant training data over the course of simulation. We demonstrate SKMD for the active learning of a neural network model of the Müller-Brown potential and the fine-tuning of a MACE interatomic potential for alanine dipeptide. Compared to active learning baselines, our method achieves higher model accuracy in fewer training iterations with the same number of acquired training samples.

Learning a Markov transition model is not merely conditional density estimation: the learned object must be a valid transition kernel before it is iterated in downstream dynamics. This paper introduces a Doeblin-anchored contrastive chart, a statistical-to-dynamical coordinate framework for learning transition kernels from contrastive objectives. Given a restart law and an anchor strength, the chart mixes the target transition with the restart law. The resulting anchored kernel is simultaneously a Doeblin-minorized Markov kernel, the positive conditional law in a binary contrastive experiment, and an explicitly invertible coordinate for the original transition law. We prove that the anchored contrastive risk identifies the anchored transition density and calibrates excess risk to density error. Since inversion of a learned score may produce a signed or unnormalized object, we introduce a measurable Markovization operator that restores kernel validity while preserving integrated $L^1$ accuracy up to a constant factor. Oracle inequalities and Hölder--ReLU approximation bounds yield nonparametric rates for independent transition pairs. For stationary geometrically $β$-mixing trajectories, a conservative thinning-and-coupling extension yields the same reconstruction interface with an effective sample size. Occupancy-weighted perturbation bounds transfer one-step kernel error to finite-horizon marginal, path-law, and occupation-measure errors under explicit coverage.