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Recent advances in generative modeling -- particularly diffusion models and flow matching -- have achieved remarkable success in synthesizing discrete data such as images and videos. However, adapting these models to physical applications…

Machine Learning · Computer Science 2025-11-26 Sifan Wang , Zehao Dou , Siming Shan , Tong-Rui Liu , Lu Lu

Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models…

Machine Learning · Computer Science 2026-01-22 Kangyu Zheng , Kai Zhang , Jiale Tan , Xuehan Chen , Yingzhou Lu , Zaixi Zhang , Lichao Sun , Marinka Zitnik , Tianfan Fu , Zhiding Liang

Diffusion alignment aims to optimize diffusion models for the downstream objective. While existing methods based on reinforcement learning or direct backpropagation achieve considerable success in maximizing rewards, they often suffer from…

Machine Learning · Computer Science 2026-03-09 Jaewoo Lee , Minsu Kim , Sanghyeok Choi , Inhyuck Song , Sujin Yun , Hyeongyu Kang , Woocheol Shin , Taeyoung Yun , Kiyoung Om , Jinkyoo Park

Inference-time controllable generation is essential for real-world applications of unconditional diffusion models. However, most existing techniques focus on individual samples, struggling in applications that require the sample population…

Machine Learning · Computer Science 2026-05-11 Hao Luan , See-Kiong Ng , Chun Kai Ling

Simultaneously optimizing multiple, frequently conflicting, molecular properties is a key bottleneck in the development of novel therapeutics. Although a promising approach, the efficacy of multi-task learning is often compromised by…

Machine Learning · Computer Science 2025-10-01 Mason Minot , Gisbert Schneider

In recent years, diffusion models have demonstrated remarkable success in high-fidelity image synthesis. However, fine-tuning these models for specialized domains, such as medical imaging, remains challenging due to limited domain-specific…

Computer Vision and Pattern Recognition · Computer Science 2025-10-28 Ruchir Namjoshi , Nagasai Thadishetty , Vignesh Kumar , Hemanth Venkateshwara

Identifying novel drug-target interactions (DTI) is a critical and rate limiting step in drug discovery. While deep learning models have been proposed to accelerate the identification process, we show that state-of-the-art models fail to…

In recent years, AI-assisted drug design methods have been proposed to generate molecules given the pockets' structures of target proteins. Most of them are atom-level-based methods, which consider atoms as basic components and generate…

Biomolecules · Quantitative Biology 2024-03-19 Haitao Lin , Yufei Huang , Odin Zhang , Lirong Wu , Siyuan Li , Zhiyuan Chen , Stan Z. Li

Diffusion models have revolutionized generative tasks through high-fidelity outputs, yet flow matching (FM) offers faster inference and empirical performance gains. However, current foundation FM models are computationally prohibitive for…

Computer Vision and Pattern Recognition · Computer Science 2025-06-04 Johannes Schusterbauer , Ming Gui , Frank Fundel , Björn Ommer

Diffusion models have achieved great success in a range of tasks, such as image synthesis and molecule design. As such successes hinge on large-scale training data collected from diverse sources, the trustworthiness of these collected data…

Machine Learning · Computer Science 2023-03-13 Weixin Chen , Dawn Song , Bo Li

Molecular foundation models are rapidly advancing scientific discovery, but their unreliability on out-of-distribution (OOD) samples severely limits their application in high-stakes domains such as drug discovery and protein design. A…

Machine Learning · Computer Science 2025-10-01 Langzhou He , Junyou Zhu , Fangxin Wang , Junhua Liu , Haoyan Xu , Yue Zhao , Philip S. Yu , Qitian Wu

Drug-target binding affinity prediction is a fundamental task for drug discovery. It has been extensively explored in literature and promising results are reported. However, in this paper, we demonstrate that the results may be misleading…

Machine Learning · Computer Science 2025-04-15 Chenbin Zhang , Zhiqiang Hu , Chuchu Jiang , Wen Chen , Jie Xu , Shaoting Zhang

Deep generative diffusion models are a promising avenue for 3D de novo molecular design in materials science and drug discovery. However, their utility is still limited by suboptimal performance on large molecular structures and limited…

Machine Learning · Computer Science 2023-11-27 Tuan Le , Julian Cremer , Frank Noé , Djork-Arné Clevert , Kristof Schütt

The Diffusion Probabilistic Model (DPM) has emerged as a highly effective generative model in the field of computer vision. Its intermediate latent vectors offer rich semantic information, making it an attractive option for various…

Computer Vision and Pattern Recognition · Computer Science 2023-03-29 Haipeng Zhou , Lei Zhu , Yuyin Zhou

This tutorial provides an in-depth guide on inference-time guidance and alignment methods for optimizing downstream reward functions in diffusion models. While diffusion models are renowned for their generative modeling capabilities,…

Artificial Intelligence · Computer Science 2025-01-22 Masatoshi Uehara , Yulai Zhao , Chenyu Wang , Xiner Li , Aviv Regev , Sergey Levine , Tommaso Biancalani

In the scope of drug discovery, the molecular design aims to identify novel compounds from the chemical space where the potential drug-like molecules are estimated to be in the order of 10^60 - 10^100. Since this search task is…

Machine Learning · Computer Science 2022-10-25 Wenlu Wang , Ye Wang , Honggang Zhao , Simone Sciabola

Molecule generation, especially generating 3D molecular geometries from scratch (i.e., 3D \textit{de novo} generation), has become a fundamental task in drug designs. Existing diffusion-based 3D molecule generation methods could suffer from…

Machine Learning · Computer Science 2022-09-14 Lei Huang , Hengtong Zhang , Tingyang Xu , Ka-Chun Wong

In many real-world regression tasks, the data distribution is heavily skewed, and models learn predominantly from abundant majority samples while failing to predict minority labels accurately. While imbalanced classification has been…

Machine Learning · Computer Science 2025-09-30 Shayan Alahyari

Diffusion models have demonstrated exceptional efficacy in various generative applications. While existing models focus on minimizing a weighted sum of denoising score matching losses for data distribution modeling, their training primarily…

Computer Vision and Pattern Recognition · Computer Science 2024-03-07 Ling Yang , Haotian Qian , Zhilong Zhang , Jingwei Liu , Bin Cui

Recently, deep neural network (DNN)-based drug-target interaction (DTI) models were highlighted for their high accuracy with affordable computational costs. Yet, the models' insufficient generalization remains a challenging problem in the…

Biomolecules · Quantitative Biology 2021-12-14 Seokhyun Moon , Wonho Zhung , Soojung Yang , Jaechang Lim , Woo Youn Kim