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Biased enhanced sampling methods utilizing collective variables (CVs) are powerful tools for sampling conformational ensembles. Due to high intrinsic dimensions, efficiently generating conformational ensembles for complex systems requires…

Machine Learning · Computer Science 2023-12-19 Yikai Liu , Tushar K. Ghosh , Guang Lin , Ming Chen

In light of the widespread success of generative models, a significant amount of research has gone into speeding up their sampling time. However, generative models are often sampled multiple times to obtain a diverse set incurring a cost…

Machine Learning · Computer Science 2023-11-27 Gabriele Corso , Yilun Xu , Valentin de Bortoli , Regina Barzilay , Tommi Jaakkola

We introduce Adjoint Sampling, a highly scalable and efficient algorithm for learning diffusion processes that sample from unnormalized densities, or energy functions. It is the first on-policy approach that allows significantly more…

We address the challenge of training diffusion models to sample from unnormalized energy distributions in the absence of data, the so-called diffusion samplers. Although these approaches have shown promise, they struggle to scale in more…

Machine Learning · Computer Science 2025-11-07 Minkyu Kim , Kiyoung Seong , Dongyeop Woo , Sungsoo Ahn , Minsu Kim

The rare-event sampling problem has long been the central limiting factor in molecular dynamics (MD), especially in biomolecular simulation. Recently, diffusion models such as BioEmu have emerged as powerful equilibrium samplers that…

As Diffusion Models have shown promising performance, a lot of efforts have been made to improve the controllability of Diffusion Models. However, how to train Diffusion Models to have the disentangled latent spaces and how to naturally…

Computer Vision and Pattern Recognition · Computer Science 2025-07-02 Wonwoong Cho , Hareesh Ravi , Midhun Harikumar , Vinh Khuc , Krishna Kumar Singh , Jingwan Lu , David I. Inouye , Ajinkya Kale

We introduce a novel, training-free method for sampling differentiable representations (diffreps) using pretrained diffusion models. Rather than merely mode-seeking, our method achieves sampling by "pulling back" the dynamics of the…

Computer Vision and Pattern Recognition · Computer Science 2024-12-11 Yash Savani , Marc Finzi , J. Zico Kolter

Sampling complex free energy surfaces is one of the main challenges of modern atomistic simulation methods. The presence of kinetic bottlenecks in such surfaces often renders a direct approach useless. A popular strategy is to identify a…

Computational Physics · Physics 2019-09-25 Luigi Bonati , Yue-Yu Zhang , Michele Parrinello

Variable selection for high-dimensional, highly correlated data has long been a challenging problem, often yielding unstable and unreliable models. We propose a resample-aggregate framework that exploits diffusion models' ability to…

Methodology · Statistics 2025-08-20 Minjie Wang , Xiaotong Shen , Wei Pan

Understanding transition pathways between two meta-stable states of a molecular system is crucial to advance drug discovery and material design. However, unbiased molecular dynamics (MD) simulations are computationally infeasible because of…

Machine Learning · Computer Science 2025-01-28 Kiyoung Seong , Seonghyun Park , Seonghwan Kim , Woo Youn Kim , Sungsoo Ahn

A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is…

Computational Physics · Physics 2024-04-09 Lukas Müllender , Andrea Rizzi , Michele Parrinello , Paolo Carloni , Davide Mandelli

The typically rugged nature of molecular free energy landscapes can frustrate efficient sampling of the thermodynamically relevant phase space due to the presence of high free energy barriers. Enhanced sampling techniques can improve phase…

Biomolecules · Quantitative Biology 2023-08-21 Nicholas S. M. Herringer , Siva Dasetty , Diya Gandhi , Junhee Lee , Andrew L. Ferguson

We review a selection of methods for performing enhanced sampling in molecular dynamics simulations. We consider methods based on collective variable biasing and on tempering, and offer both historical and contemporary perspectives. In…

Statistical Mechanics · Physics 2014-01-03 Cameron Abrams , Giovanni Bussi

We introduce Diffusion Active Learning, a novel approach that combines generative diffusion modeling with data-driven sequential experimental design to adaptively acquire data for inverse problems. Although broadly applicable, we focus on…

Machine Learning · Computer Science 2025-04-07 Luis Barba , Johannes Kirschner , Tomas Aidukas , Manuel Guizar-Sicairos , Benjamín Béjar

Enhanced sampling methods are indispensable in computational physics and chemistry, where atomistic simulations cannot exhaustively sample the high-dimensional configuration space of dynamical systems due to the sampling problem. A class of…

Chemical Physics · Physics 2024-04-04 Jakub Rydzewski , Ming Chen , Tushar K. Ghosh , Omar Valsson

Diffusion models have demonstrated remarkable efficacy in generating high-quality samples. Existing diffusion-based image restoration algorithms exploit pre-trained diffusion models to leverage data priors, yet they still preserve elements…

Image and Video Processing · Electrical Eng. & Systems 2024-08-07 Hongjie Wu , Linchao He , Mingqin Zhang , Dongdong Chen , Kunming Luo , Mengting Luo , Ji-Zhe Zhou , Hu Chen , Jiancheng Lv

Diffusion models have emerged as powerful tools for generative tasks, producing high-quality outputs across diverse domains. However, how the generated data responds to the initial noise perturbation in diffusion models remains…

Machine Learning · Computer Science 2025-02-10 Bowen Song , Zecheng Zhang , Zhaoxu Luo , Jason Hu , Wei Yuan , Jing Jia , Zhengxu Tang , Guanyang Wang , Liyue Shen

Rare event sampling is a central problem in modern computational chemistry research. Among the existing methods, transition path sampling (TPS) can generate unbiased representations of reaction processes. However, its efficiency depends on…

Computational Physics · Physics 2024-04-04 Jintu Zhang , Odin Zhang , Luigi Bonati , TingJun Hou

Macromolecular and biomolecular folding landscapes typically contain high free energy barriers that impede efficient sampling of configurational space by standard molecular dynamics simulation. Biased sampling can artificially drive the…

Biological Physics · Physics 2018-11-01 Wei Chen , Andrew L Ferguson

Diffusion models excel at capturing the natural design spaces of images, molecules, DNA, RNA, and protein sequences. However, rather than merely generating designs that are natural, we often aim to optimize downstream reward functions while…

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