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The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini

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

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

With the emergence of diffusion models as a frontline generative model, many researchers have proposed molecule generation techniques with conditional diffusion models. However, the unavoidable discreteness of a molecule makes it difficult…

Machine Learning · Computer Science 2025-06-05 Jinho Chang , Jong Chul Ye

We propose LOGDIFF (Logical Guidance for the Exact Composition of Diffusion Models), a guidance framework for diffusion models that enables principled constrained generation with complex logical expressions at inference time. We study when…

Machine Learning · Computer Science 2026-03-24 Francesco Alesiani , Jonathan Warrell , Tanja Bien , Henrik Christiansen , Matheus Ferraz , Mathias Niepert

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

Proteins adopt multiple structural conformations to perform their diverse biological functions, and understanding these conformations is crucial for advancing drug discovery. Traditional physics-based simulation methods often struggle with…

Biomolecules · Quantitative Biology 2025-03-14 Jiarui Lu , Xiaoyin Chen , Stephen Zhewen Lu , Chence Shi , Hongyu Guo , Yoshua Bengio , Jian Tang

In recent years, deep learning techniques have made significant strides in molecular generation for specific targets, driving advancements in drug discovery. However, existing molecular generation methods present significant limitations:…

Machine Learning · Computer Science 2025-03-12 Taojie Kuang , Qianli Ma , Athanasios V. Vasilakos , Yu Wang , Qiang , Cheng , Zhixiang Ren

Structure-Based Drug Design (SBDD) aims to discover bioactive ligands. Conventional approaches construct probability paths separately in Euclidean and probabilistic spaces for continuous atomic coordinates and discrete chemical categories,…

Machine Learning · Computer Science 2026-05-26 Yaowei Jin , Junjie Wang , Cheng Cao , Penglei Wang , Duo An , Qian Shi

Shape-based virtual screening is widely employed in ligand-based drug design to search chemical libraries for molecules with similar 3D shapes yet novel 2D chemical structures compared to known ligands. 3D deep generative models have the…

Chemical Physics · Physics 2022-10-12 Keir Adams , Connor W. Coley

Autoregressive models excel in modeling sequential dependencies by enforcing causal constraints, yet they struggle to capture complex bidirectional patterns due to their unidirectional nature. In contrast, mask-based models leverage…

Computation and Language · Computer Science 2024-09-18 S. Rohollah Hosseyni , Ali Ahmad Rahmani , S. Jamal Seyedmohammadi , Sanaz Seyedin , Arash Mohammadi

Recent advances in generative models, particularly diffusion and auto-regressive models, have revolutionized fields like computer vision and natural language processing. However, their application to structure-based drug design (SBDD)…

Machine Learning · Computer Science 2025-07-29 Yi He , Ailun Wang , Zhi Wang , Yu Liu , Xingyuan Xu , Wen Yan

Structure-based drug design (SBDD) aims to discover drug candidates by finding molecules (ligands) that bind tightly to a disease-related protein (targets), which is the primary approach to computer-aided drug discovery. Recently, applying…

Quantitative Methods · Quantitative Biology 2022-12-01 Tianfan Fu , Wenhao Gao , Connor W. Coley , Jimeng Sun

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

When reliable target structures are unavailable at scale or phenotypes arise from dysregulated pathways, transcriptomic perturbations provide a system-level functional readout for drug action. In this work, we formalize…

Machine Learning · Computer Science 2026-05-18 Ziyu Xu , Zijian Zhang , Liang Wang , Zhiyuan Liu , Qiang Liu , Shu Wu , Liang Wang

Equivocal 3D lesion segmentation exhibits high inter-observer variability. Conventional deterministic models ignore this aleatoric uncertainty, producing over-confident masks that obscure clinical risks. Conversely, while generative methods…

Computer Vision and Pattern Recognition · Computer Science 2026-03-05 Chao Wu , Kangxian Xie , Mingchen Gao

We introduce AbDiffuser, an equivariant and physics-informed diffusion model for the joint generation of antibody 3D structures and sequences. AbDiffuser is built on top of a new representation of protein structure, relies on a novel…

Goal-directed molecular generation requires satisfying heterogeneous constraints such as protein--ligand compatibility and multi-objective drug-like properties, yet existing methods often optimize these constraints in isolation, failing to…

Machine Learning · Computer Science 2026-04-14 Yanting Li , Zhuoyang Jiang , Enyan Dai , Lei Wang , Wen-Cai Ye , Li Liu

In this paper, we present DesignDiffusion, a simple yet effective framework for the novel task of synthesizing design images from textual descriptions. A primary challenge lies in generating accurate and style-consistent textual and visual…

Computer Vision and Pattern Recognition · Computer Science 2025-03-04 Zhendong Wang , Jianmin Bao , Shuyang Gu , Dong Chen , Wengang Zhou , Houqiang Li

Low-field to high-field MRI synthesis has emerged as a cost-effective strategy to enhance image quality under hardware and acquisition constraints, particularly in scenarios where access to high-field scanners is limited or impractical.…

Computer Vision and Pattern Recognition · Computer Science 2026-03-13 Zhenxuan Zhang , Peiyuan Jing , Ruicheng Yuan , Liwei Hu , Anbang Wang , Fanwen Wang , Yinzhe Wu , Kh Tohidul Islam , Zhaolin Chen , Zi Wang , Peter Lally , Guang Yang
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