Scalable Inference-Time Annealing for Continuous Normalizing Flows

Daniel Peñaherrera, Rishal Aggarwal, David Ryan Koes

Keywords: Flows, EBMs, Boltzmann Generators, Annealing, Molecular Ensembles

TL;DR: Enabling scalable molecular sampling via learned likelihoods and flow annealing.

Abstract: A long standing challenge in computational chemistry and biophysics is efficiently sampling the Boltzmann distribution of molecules. Advances in generative modeling have been proposed to address the limitations of conventional sampling techniques by eliminating the computational cost of simulation. A promising direction is iteratively finetuning diffusion models along a temperature ladder whereby training data is generated via importance sampling during inference-time annealing. Unfortunately, these methods require computing a divergence over the score field to estimate importance weights, rendering them intractable for larger systems. Here we present scalable inference-time annealing (SITA), which retrains flow-based models to generate samples at progressively lower temperatures using an energy-based model to facilitate fast surrogate likelihoods. We demonstrate start-of-the-art performance on both alanine dipeptide and alanine tripeptide while avoiding costly divergence terms and using nearly 2 orders of magnitude fewer energy evaluations.

Submission Number: 84