A Doeblin-Anchored Contrastive Chart for Learning Markov Transition Kernels

Most molecular transitions occur on timescales far beyond direct molecular dynamics simulations. The committor, the probability that a configuration reaches a product state before a reactant state, is a central kinetic statistic, providing a mechanism-independent reaction coordinate and a foundation for transition path theory and the calculation of rates. This review surveys modern approaches for estimating the committor and related kinetic statistics from molecular simulations, with an emphasis on self-supervised methods that learn solutions of their defining dynamical equations rather than relying on labeled shooting data. We develop a common operator viewpoint connecting generator-based partial differential equations, variational principles, Markov state models, dynamical Galerkin approximation, and neural networks. Empirical and theoretical evidence points to the efficiency of these methods. We provide theoretical and practical guidance for realizing their full potential in applications, including strategies for treating non-Markovian effects and for sampling. We conclude by identifying opportunities for further research, including connections to reinforcement learning and generative modeling.

Engression is a recently proposed and effective framework for conditional distribution learning. Its multi-step Reverse Markov extension further improves generative flexibility by decomposing complex conditional sampling into sequential reverse transitions. Despite their strong empirical performance, rigorous finite-sample statistical guarantees for these methods remain unavailable. In this paper, under deep neural network parameterizations, we establish nonasymptotic convergence bounds for Engression by directly controlling the Energy Distance between the learned and target conditional distributions. For the Reverse Markov framework, we further develop an Energy-Distance-based chain rule that enables a rigorous analysis of error propagation across reverse steps. Our analysis yields corresponding excess-risk bounds that are near-optimal up to logarithmic factors relative to the classical minimax rate over a general Hölder class.

MeanFlow enables one-step generation in continuous spaces by learning an average velocity over a time interval rather than the instantaneous velocity field of flow matching. However, discrete state spaces do not have smooth trajectories or spatial derivatives, so the continuous formulation does not directly apply. We introduce Discrete MeanFlow, which replaces the motion of a point with the transport of probability mass over finite states. Our key object is the conditional transition kernel of a continuous-time Markov chain (CTMC), from which we define a mean discrete rate that measures the average change in transition probability over a time interval. We prove a Discrete MeanFlow identity that relates this finite-interval rate to the instantaneous CTMC generator at the endpoint, with the Kolmogorov forward equation replacing the spatial chain rule of continuous MeanFlow. Based on this identity, we parameterize the transition kernel directly using a boundary-by-construction design that guarantees valid probability outputs and exact boundary conditions without auxiliary losses. Since the learned kernel is itself a probability distribution, generation reduces to a single forward pass followed by one categorical draw meaning no iterative denoising, ODE integration, or multi-step refinement is required. We validate the framework on exact finite-state Markov chains, where the learned kernel recovers the analytical ground truth to high precision, and on factorized synthetic sequence generation tasks with varying alphabet sizes and sequence lengths.