James Matthew Young | Searcharxiv

arXiv2026

Diffusion Path Samplers via Sequential Monte Carlo

We develop diffusion-based samplers for target distributions known up to a normalising constant. To this end, we rely on the well-known diffusion path that smoothly interpolates between a simple base distribution and the target, popularised by diffusion models. We tackle the score estimation problem by developing an efficient sequential Monte Carlo sampler that evolves auxiliary variables from conditional distributions along the path, providing principled score and density estimates for time-varying distributions. To control the variance of score estimates, we further propose practical control variate schedules that incur minimal overhead. We adapt this general framework to paths induced by the Ornstein-Uhlenbeck (OU) time-reversal process, stochastic interpolants, and diffusion annealed Langevin dynamics, outlining their trade-offs. Finally, we provide theoretical guarantees and empirically demonstrate the effectiveness of our method on several synthetic and real-world datasets.

stat.ML↗

arXiv2025

On diffusion posterior sampling via sequential Monte Carlo for zero-shot scaffolding of protein motifs

With the advent of diffusion models, new proteins can be generated at an unprecedented rate. The motif scaffolding problem requires steering this generative process to yield proteins with a desirable functional substructure called a motif. While models have been trained to take the motif as conditional input, recent techniques in diffusion posterior sampling can be leveraged as zero-shot alternatives whose approximations can be corrected with sequential Monte Carlo (SMC) algorithms. In this work, we introduce a new set of guidance potentials for describing scaffolding tasks and solve them by adapting SMC-aided diffusion posterior samplers with an unconditional model, Genie, as a prior. In single motif problems, we find that (i) the proposed potentials perform comparably, if not better, than the conventional masking approach, (ii) samplers based on reconstruction guidance outperform their replacement method counterparts, and (iii) measurement tilted proposals and twisted targets improve performance substantially. Furthermore, as a demonstration, we provide solutions to two multi-motif problems by pairing reconstruction guidance with an SE(3)-invariant potential. We also produce designable internally symmetric monomers with a guidance potential for point symmetry constraints. Our code is available at: https://github.com/matsagad/mres-project.

q-bio.BM↗