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Designing 3D ligands within a target binding site is a fundamental task in drug discovery. Existing structured-based drug design methods treat all ligand atoms equally, which ignores different roles of atoms in the ligand for drug design…

Biomolecules · Quantitative Biology 2024-03-14 Jiaqi Guan , Xiangxin Zhou , Yuwei Yang , Yu Bao , Jian Peng , Jianzhu Ma , Qiang Liu , Liang Wang , Quanquan Gu

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Generating ligand molecules for specific protein targets, known as structure-based drug design, is a fundamental problem in therapeutics development and biological discovery. Recently, target-aware generative models, especially diffusion…

Biomolecules · Quantitative Biology 2024-10-29 Siyi Gu , Minkai Xu , Alexander Powers , Weili Nie , Tomas Geffner , Karsten Kreis , Jure Leskovec , Arash Vahdat , Stefano Ermon

Effective generation of molecular structures, or new chemical entities, that bind to target proteins is crucial for lead identification and optimization in drug discovery. Despite advancements in atom- and motif-wise deep learning models…

Machine Learning · Computer Science 2025-03-04 Guanlue Li , Chenran Jiang , Ziqi Gao , Yu Liu , Chenyang Liu , Jiean Chen , Yong Huang , Jia Li

Developing bioactive molecules remains a central, time- and cost-heavy challenge in drug discovery, particularly for novel targets lacking structural or functional data. Pharmacophore modeling presents an alternative for capturing the key…

Machine Learning · Computer Science 2025-05-16 Amira Alakhdar , Barnabas Poczos , Newell Washburn

Structure-based drug design (SBDD), which aims to generate molecules that can bind tightly to the target protein, is an essential problem in drug discovery, and previous approaches have achieved initial success. However, most existing…

Machine Learning · Computer Science 2024-04-04 Xinze Li , Penglei Wang , Tianfan Fu , Wenhao Gao , Chengtao Li , Leilei Shi , Junhong Liu

Molecular representation learning has shown great success in advancing AI-based drug discovery. The core of many recent works is based on the fact that the 3D geometric structure of molecules provides essential information about their…

Machine Learning · Computer Science 2024-10-23 Jiying Zhang , Zijing Liu , Yu Wang , Yu Li

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

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Structure-Based Drug Design (SBDD) has revolutionized drug discovery by enabling the rational design of molecules for specific protein targets. Despite significant advancements in improving docking scores, advanced 3D-SBDD generative models…

Biomolecules · Quantitative Biology 2025-03-04 Bowen Gao , Yanwen Huang , Yiqiao Liu , Wenxuan Xie , Wei-Ying Ma , Ya-Qin Zhang , Yanyan Lan

Recent remarkable advancements in geometric deep generative models, coupled with accumulated structural data, enable structure-based drug design (SBDD) using only target protein information. However, existing models often struggle to…

Biomolecules · Quantitative Biology 2026-03-09 Joongwon Lee , Wonho Zhung , Jisu Seo , Woo Youn Kim

Achieving precise control over a molecule's biological activity-encompassing targeted activation/inhibition, cooperative multi-target modulation, and off-target toxicity mitigation-remains a critical challenge in de novo drug design.…

Machine Learning · Computer Science 2025-08-11 Renyi Zhou , Huimin Zhu , Jing Tang , Min Li

The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

Nuclei appear small in size, yet, in real clinical practice, the global spatial information and correlation of the color or brightness contrast between nuclei and background, have been considered a crucial component for accurate nuclei…

Image and Video Processing · Electrical Eng. & Systems 2023-07-18 Zhenqi He , Mathias Unberath , Jing Ke , Yiqing Shen

In this work, we propose a mutual information (MI) based unsupervised domain adaptation (UDA) method for the cross-domain nuclei segmentation. Nuclei vary substantially in structure and appearances across different cancer types, leading to…

Computer Vision and Pattern Recognition · Computer Science 2022-06-30 Yash Sharma , Sana Syed , Donald E. Brown

Predicting drug-target affinity is fundamental to virtual screening and lead optimization. However, existing deep models often suffer from representation collapse in stringent cold-start regimes, where the scarcity of labels and domain…

Machine Learning · Statistics 2026-03-13 Yining Qian , Pengjie Wang , Yixiao Li , An-Yang Lu , Cheng Tan , Shuang Li , Lijun Liu

Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a…

Machine Learning · Computer Science 2017-03-31 Joseph Gomes , Bharath Ramsundar , Evan N. Feinberg , Vijay S. Pande

Structure-based drug design (SBDD) aims to efficiently discover high-affinity ligands within vast chemical spaces. However, current generative models struggle with objective misalignment and rigid sampling budgets. We present MolFORM, a…

Computational Engineering, Finance, and Science · Computer Science 2026-02-26 Daiheng Zhang , Zhao Zhang
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