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Molecule generation is a very important practical problem, with uses in drug discovery and material design, and AI methods promise to provide useful solutions. However, existing methods for molecule generation focus either on 2D graph…

Machine Learning · Computer Science 2024-02-07 Chenqing Hua , Sitao Luan , Minkai Xu , Rex Ying , Jie Fu , Stefano Ermon , Doina Precup

The design of novel protein structures remains a challenge in protein engineering for applications across biomedicine and chemistry. In this line of work, a diffusion model over rigid bodies in 3D (referred to as frames) has shown success…

Machine Learning · Computer Science 2023-05-24 Jason Yim , Brian L. Trippe , Valentin De Bortoli , Emile Mathieu , Arnaud Doucet , Regina Barzilay , Tommi Jaakkola

Antibodies are essential proteins responsible for immune responses in organisms, capable of specifically recognizing antigen molecules of pathogens. Recent advances in generative models have significantly enhanced rational antibody design.…

Artificial Intelligence · Computer Science 2025-11-10 Zichen Wang , Yaokun Ji , Jianing Tian , Shuangjia Zheng

Protein interaction modeling is central to protein design, which has been transformed by machine learning with applications in drug discovery and beyond. In this landscape, structure-based de novo binder design is cast as either conditional…

Block Diffusion Models (BDMs) support parallel generation, flexible-length output, and KV caching, making them promising for efficient document parsing. However, existing BDMs bind denoising and cache commitment to fixed block boundaries:…

Computer Vision and Pattern Recognition · Computer Science 2026-05-19 Mingxu Chai , Ziyu Shen , Chenyu Liu , Kaidi Zhang , Jiazheng Zhang , Dingwei Zhu , Zhiheng Xi , Ruoyu Chen , Jun Long , Jihua Kang , Tao Gui , Qi Zhang

Generative AI has the potential to revolutionize drug discovery. Yet, despite recent advances in deep learning, existing models cannot generate molecules that satisfy all desired physicochemical properties. Herein, we describe IDOLpro, a…

Chemical Physics · Physics 2025-04-29 Amit Kadan , Kevin Ryczko , Erika Lloyd , Adrian Roitberg , Takeshi Yamazaki

The integration of deep learning, particularly AI-Generated Content, with high-quality data derived from ab initio calculations has emerged as a promising avenue for transforming the landscape of scientific research. However, the challenge…

Machine Learning · Computer Science 2024-12-11 Kaiwei Zhang , Yange Lin , Guangcheng Wu , Yuxiang Ren , Xuecang Zhang , Bo wang , Xiaoyu Zhang , Weitao Du

Designing mechanical linkages to achieve target end-effector trajectories presents a fundamental challenge due to the intricate coupling between continuous node placements, discrete topological configurations, and nonlinear kinematic…

Machine Learning · Computer Science 2026-01-08 Yayati Jadhav , Amir Barati Farimani

The recent breakthrough of AlphaFold3 in modeling complex biomolecular interactions, including those between proteins and ligands, nucleotides, or metal ions, creates new opportunities for protein design. In so-called inverse protein…

Biomolecules · Quantitative Biology 2025-07-22 Kai Yi , Kiarash Jamali , Sjors H. W. Scheres

Probabilistic denoising diffusion models (DDMs) have set a new standard for 2D image generation. Extending DDMs for 3D content creation is an active field of research. Here, we propose TetraDiffusion, a diffusion model that operates on a…

Computer Vision and Pattern Recognition · Computer Science 2024-08-12 Nikolai Kalischek , Torben Peters , Jan D. Wegner , Konrad Schindler

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

Synthesizability remains a critical bottleneck in generative molecular design. While recent advances have addressed synthesizability in 2D graphs, extending these constraints to 3D for geometry-based conditional generation remains largely…

Despite the exciting progress in target-specific de novo protein binder design, peptide binder design remains challenging due to the flexibility of peptide structures and the scarcity of protein-peptide complex structure data. In this…

Biomolecules · Quantitative Biology 2024-09-04 Fanhao Wang , Yuzhe Wang , Laiyi Feng , Changsheng Zhang , Luhua Lai

This paper introduces diffusion protein language model (DPLM), a versatile protein language model that demonstrates strong generative and predictive capabilities for protein sequences. We first pre-train scalable DPLMs from…

Machine Learning · Computer Science 2024-10-17 Xinyou Wang , Zaixiang Zheng , Fei Ye , Dongyu Xue , Shujian Huang , Quanquan Gu

Peptide design plays a pivotal role in therapeutics, allowing brand new possibility to leverage target binding sites that are previously undruggable. Most existing methods are either inefficient or only concerned with the target-agnostic…

Biomolecules · Quantitative Biology 2024-10-31 Xiangzhe Kong , Yinjun Jia , Wenbing Huang , Yang Liu

The generation of ligands that both are tailored to a given protein pocket and exhibit a range of desired chemical properties is a major challenge in structure-based drug design. Here, we propose an in-silico approach for the $\textit{de…

Biomolecules · Quantitative Biology 2024-05-27 Julian Cremer , Tuan Le , Frank Noé , Djork-Arné Clevert , Kristof T. Schütt

The de novo generation of molecules with targeted properties is crucial in biology, chemistry, and drug discovery. Current generative models are limited to using single property values as conditions, struggling with complex customizations…

Machine Learning · Computer Science 2024-10-08 Yanchen Luo , Junfeng Fang , Sihang Li , Zhiyuan Liu , Jiancan Wu , An Zhang , Wenjie Du , Xiang Wang

Structure-based drug design (SBDD), which maps target proteins to candidate molecular ligands, is a fundamental task in drug discovery. Effectively aligning protein structural representations with molecular representations, and ensuring…

Artificial Intelligence · Computer Science 2025-11-03 Wei Zhang , Zekun Guo , Yingce Xia , Peiran Jin , Shufang Xie , Tao Qin , Xiang-Yang Li

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…

Comprehending the long-timescale dynamics of protein-ligand complexes is very important for drug discovery and structural biology, but it continues to be computationally challenging for large biomolecular systems. We introduce…

Biomolecules · Quantitative Biology 2025-08-26 Rakesh Thakur , Riya Gupta