METALICA is a new method that combines Metadynamics with Replica Exchange on pretrained diffusion models to improve sampling of rare conformational states in proteins. It builds a bias potential along a chosen Collective Variable, pushes new samples away from previously visited ones, and reweights them to recover the unbiased distribution. By running one replica per diffusion level and allowing inter‑replica communication, METALICA can generate long Markov chains that uncover rare events, as demonstrated on a bimodal test system and on protein unfolding where it reveals a second free‑energy minimum that other methods miss.
By Alireza Omidi, Jiajun He, J\"org Gsponer, Saifuddin Syed
arXiv:2503. 14549v4 Announce Type: replace Abstract: Scientific generative models must turn tractable local decisions into globally correlated samples that respect physical constraints.
By Michael Chertkov, Hamidreza Behjoo, Sungsoo Ahn
arXiv:2604. 13213v2 Announce Type: replace-cross Abstract: Rare events such as conformational changes in biomolecules, phase transitions, and chemical reactions are central to the behavior of many physical systems, yet they are extremely difficult to study computationally because unbiased simulations seldom produce them.
By Yuanqi Du, Jiajun He, Dinghuai Zhang, Eric Vanden-Eijnden, Carles Domingo-Enrich
arXiv:2608. 13800v1 Announce Type: new Abstract: Transition path sampling (TPS) aims to efficiently generate rare molecular transition trajectories between metastable states and is essential for understanding biomolecular mechanisms.
By Jingqian Liu, Yu-Hsiang Wang, Yanru Qu, Ge Liu
The paper introduces the Energy-based Feynman-Kac Corrector (EBFKC), a method that improves inference-time scaling for diffusion models that are imperfect due to data and training limitations. EBFKC derives Feynman-Kac dynamics to exactly track a prescribed path in continuous time, then approximates these dynamics with sequential Monte Carlo and variance‑controlling guidance. Experiments on Gaussian mixtures, particle systems, and molecular simulations demonstrate that EBFKC closely matches target distributions and free‑energy profiles, outperforming standard inference‑time scaling baselines that still exhibit significant sampling errors.
By Zuokai Wen, Louis Grenioux, Weinan E, Jiequn Han
arXiv:2609.37043v1 Announce Type: new
Abstract: Sampling from unnormalized distributions over large discrete state spaces becomes difficult when a multimodal target is far from a tractable reference....
By Yuwen Qian, Yidong Ouyang, Zhengyan Wan, Hongyuan Zha
arXiv:2609.35947v1 Announce Type: new
Abstract: Many inference-time tasks for pretrained discrete diffusion models and diffusion language models reduce to drawing samples from a tilted version of the...
By Yinuo Ren, Haoxuan Chen, Grant M. Rotskoff, Jiequn Han, Lexing Ying
arXiv:2607. 15682v1 Announce Type: new Abstract: Sampling from an unnormalized Boltzmann density requires proposals that move probability mass globally while retaining enough path-probability information for statistical correction.
By Moxian Qian
The paper introduces a method for specificity‑aware diffusion steering that suppresses undesired samples while preserving desired ones. By formulating the problem as a target‑design task, it derives a time‑dependent target distribution based on overlap between positive and negative reference distributions, and samples from it using a variance‑reduced Sequential Monte Carlo (SMC) sampler. Experiments on synthetic, class‑contrastive, text‑to‑image, and peptide‑MHC tasks demonstrate reduced mode shift, improved sampling stability, and better suppression of undesired regions compared to negative‑guidance baselines.
By Luran Wang, Linrui Ma, Hannes St\"ark, Regina Barzilay
arXiv:2604. 17838v2 Announce Type: replace Abstract: Generative modeling within constrained sets is essential for scientific and engineering applications involving physical, geometric, or safety requirements (e.
By Kijung Jeon, Michael Muehlebach, Molei Tao
arXiv:2608.25631v1 Announce Type: cross
Abstract: Continuous-time Markov chains (CTMCs) provide the backbone for modeling discrete stochastic dynamics across applied, physical, and biological science...
By Jose M. G. Vilar, Leonor Saiz
arXiv:2503. 14549v3 Announce Type: replace-cross Abstract: How can a cheap but biased sequential, finite-horizon sampler over a discrete space be corrected so that its terminal output follows a prescribed Gibbs distribution?
By Michael Chertkov, Sungsoo Ahn, Hamidreza Behjoo