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3D generative models have shown significant promise in structure-based drug design (SBDD), particularly in discovering ligands tailored to specific target binding sites. Existing algorithms often focus primarily on ligand-target binding,…

Deep generative models are rapidly advancing structure-based drug design, offering substantial promise for generating small molecule ligands that bind to specific protein targets. However, most current approaches assume a rigid protein…

Biomolecules · Quantitative Biology 2025-11-19 Xinzhe Zheng , Shiyu Jiang , Gustavo Seabra , Chenglong Li , Yanjun Li

Ligand-based drug design aims to identify novel drug candidates of similar shapes with known active molecules. In this paper, we formulated an in silico shape-conditioned molecule generation problem to generate 3D molecule structures…

Machine Learning · Computer Science 2023-10-18 Ziqi Chen , Bo Peng , Srinivasan Parthasarathy , Xia Ning

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

Structure-based drug design (SBDD) aims to design small-molecule ligands that bind with high affinity and specificity to pre-determined protein targets. Generative SBDD methods leverage structural data of drugs in complex with their protein…

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

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Structure-based drug design involves finding ligand molecules that exhibit structural and chemical complementarity to protein pockets. Deep generative methods have shown promise in proposing novel molecules from scratch (de-novo design),…

Quantitative Methods · Quantitative Biology 2021-11-09 Pavol Drotár , Arian Rokkum Jamasb , Ben Day , Cătălina Cangea , Pietro Liò

Generative models for molecules based on sequential line notation (e.g. SMILES) or graph representation have attracted an increasing interest in the field of structure-based drug design, but they struggle to capture important 3D spatial…

Machine Learning · Computer Science 2023-12-12 Wei Feng , Lvwei Wang , Zaiyun Lin , Yanhao Zhu , Han Wang , Jianqiang Dong , Rong Bai , Huting Wang , Jielong Zhou , Wei Peng , Bo Huang , Wenbiao Zhou

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

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Structure-based drug design has seen significant advancements with the integration of artificial intelligence (AI), particularly in the generation of hit and lead compounds. However, most AI-driven approaches neglect the importance of…

Machine Learning · Computer Science 2025-11-10 Xinheng He , Yijia Zhang , Haowei Lin , Xingang Peng , Xiangzhe Kong , Mingyu Li , Jianzhu Ma

Recently, 3D generative models have shown promising performances in structure-based drug design by learning to generate ligands given target binding sites. However, only modeling the target-ligand distribution can hardly fulfill one of the…

Biomolecules · Quantitative Biology 2024-03-22 Xiangxin Zhou , Xiwei Cheng , Yuwei Yang , Yu Bao , Liang Wang , Quanquan Gu

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

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

Generating molecules that bind to specific protein targets via diffusion models has shown good promise for structure-based drug design and molecule optimization. Especially, the diffusion models with binding interaction guidance enables…

Machine Learning · Computer Science 2025-05-12 Anjie Qiao , Hao Zhang , Qianmu Yuan , Qirui Deng , Jingtian Su , Weifeng Huang , Huihao Zhou , Guo-Bo Li , Zhen Wang , Jinping Lei

Finding drug-like compounds with high bioactivity is essential for drug discovery, but the task is complicated by the high cost of chemical synthesis and validation. With their outstanding performance in de novo drug design, deep generative…

Quantitative Methods · Quantitative Biology 2023-01-03 Yibo Li , Jianfeng Pei , Luhua Lai

Structure-based drug design (SBDD), which aims to generate 3D ligand molecules binding to target proteins, is a fundamental task in drug discovery. Existing SBDD methods typically treat protein as rigid and neglect protein structural change…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Mengdi Wang , Qi Liu

Molecular optimization, aimed at improving binding affinity or other molecular properties, is a crucial task in drug discovery that often relies on the expertise of medicinal chemists. Recently, deep learning-based 3D generative models…

Machine Learning · Computer Science 2025-05-01 Anjie Qiao , Junjie Xie , Weifeng Huang , Hao Zhang , Jiahua Rao , Shuangjia Zheng , Yuedong Yang , Zhen Wang , Guo-Bo Li , Jinping Lei

Diffusion models have emerged as powerful tools for molecular generation, particularly in the context of 3D molecular structures. Inspired by non-equilibrium statistical physics, these models can generate 3D molecular structures with…

Chemical Physics · Physics 2025-05-16 Amira Alakhdar , Barnabas Poczos , Newell Washburn
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