English

Doob's Lagrangian: A Sample-Efficient Variational Approach to Transition Path Sampling

Machine Learning 2024-12-11 v4 Artificial Intelligence Biological Physics Chemical Physics

Abstract

Rare event sampling in dynamical systems is a fundamental problem arising in the natural sciences, which poses significant computational challenges due to an exponentially large space of trajectories. For settings where the dynamical system of interest follows a Brownian motion with known drift, the question of conditioning the process to reach a given endpoint or desired rare event is definitively answered by Doob's h-transform. However, the naive estimation of this transform is infeasible, as it requires simulating sufficiently many forward trajectories to estimate rare event probabilities. In this work, we propose a variational formulation of Doob's h-transform as an optimization problem over trajectories between a given initial point and the desired ending point. To solve this optimization, we propose a simulation-free training objective with a model parameterization that imposes the desired boundary conditions by design. Our approach significantly reduces the search space over trajectories and avoids expensive trajectory simulation and inefficient importance sampling estimators which are required in existing methods. We demonstrate the ability of our method to find feasible transition paths on real-world molecular simulation and protein folding tasks.

Keywords

Cite

@article{arxiv.2410.07974,
  title  = {Doob's Lagrangian: A Sample-Efficient Variational Approach to Transition Path Sampling},
  author = {Yuanqi Du and Michael Plainer and Rob Brekelmans and Chenru Duan and Frank Noé and Carla P. Gomes and Alán Aspuru-Guzik and Kirill Neklyudov},
  journal= {arXiv preprint arXiv:2410.07974},
  year   = {2024}
}

Comments

Accepted as Spotlight at Conference on Neural Information Processing Systems (NeurIPS 2024); Alanine dipeptide results updated after fixing unphysical parameterization and energy computation

R2 v1 2026-06-28T19:16:18.535Z