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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

Deep generative models are attracting great attention for molecular design with desired properties. Most existing models generate molecules by sequentially adding atoms. This often renders generated molecules with less correlation with…

Machine Learning · Computer Science 2021-11-29 Seonghwan Seo , Jaechang Lim , Woo Youn Kim

Deep generative models have achieved tremendous success in designing novel drug molecules in recent years. A new thread of works have shown the great potential in advancing the specificity and success rate of in silico drug design by…

Machine Learning · Computer Science 2025-07-14 Xingang Peng , Shitong Luo , Jiaqi Guan , Qi Xie , Jian Peng , Jianzhu Ma

Generative models see increasing use in computer-aided drug design. However, while performing well at capturing distributions of molecular motifs, they often produce synthetically inaccessible molecules. To address this, we introduce…

Structure determination is essential to a mechanistic understanding of diseases and the development of novel therapeutics. Machine-learning-based structure prediction methods have made significant advancements by computationally predicting…

Recently, deep generative models have revealed itself as a promising way of performing de novo molecule design. However, previous research has focused mainly on generating SMILES strings instead of molecular graphs. Although current graph…

Quantitative Methods · Quantitative Biology 2018-04-24 Yibo Li , Liangren Zhang , Zhenming Liu

Structure-based drug design (SBDD) leverages the three-dimensional geometry of proteins to identify potential drug candidates. Traditional approaches, rooted in physicochemical modeling and domain expertise, are often resource-intensive.…

Quantitative Methods · Quantitative Biology 2024-11-19 Zaixi Zhang , Jiaxian Yan , Yining Huang , Qi Liu , Enhong Chen , Mengdi Wang , Marinka Zitnik

Recent advances in generative deep learning have transformed small molecule design, but most methods lack biological systems context, focusing narrowly on specific protein pockets. We introduce a non-differentiable diffusion guidance method…

Biomolecules · Quantitative Biology 2024-10-15 Vincent D. Zaballa , Elliot E. Hui

The strict selectivity of the blood-brain barrier (BBB) represents one of the most formidable challenges to successful central nervous system (CNS) drug delivery. Computational methods to generate BBB permeable drugs in silico may be…

Biomolecules · Quantitative Biology 2024-07-02 Ayush Noori , Iñaki Arango , William E. Byrd , Nada Amin

Recent advancements in structure-based drug design (SBDD) have significantly enhanced the efficiency and precision of drug discovery by generating molecules tailored to bind specific protein pockets. Despite these technological strides,…

Biomolecules · Quantitative Biology 2024-06-14 Bowen Gao , Haichuan Tan , Yanwen Huang , Minsi Ren , Xiao Huang , Wei-Ying Ma , Ya-Qin Zhang , Yanyan Lan

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

Deep learning has proven to yield fast and accurate predictions of quantum-chemical properties to accelerate the discovery of novel molecules and materials. As an exhaustive exploration of the vast chemical space is still infeasible, we…

Machine Learning · Statistics 2020-01-10 Niklas W. A. Gebauer , Michael Gastegger , Kristof T. Schütt

The ultimate goal of drug design is to find novel compounds with desirable pharmacological properties. Designing molecules retaining particular scaffolds as the core structures of the molecules is one of the efficient ways to obtain…

Quantitative Methods · Quantitative Biology 2019-09-06 Yibo Li , Jianxing Hu , Yanxing Wang , Jielong Zhou , Liangren Zhang , Zhenming Liu

Structure-based drug design (SBDD) stands at the forefront of drug discovery, emphasizing the creation of molecules that target specific binding pockets. Recent advances in this area have witnessed the adoption of deep generative models and…

Quantitative Methods · Quantitative Biology 2023-11-22 Minsi Ren , Bowen Gao , Bo Qiang , Yanyan Lan

The integration of artificial intelligence (AI) in early-stage drug discovery offers unprecedented opportunities for exploring chemical space and accelerating hit-to-lead optimization. However, docking optimization in generative approaches…

Quantitative Methods · Quantitative Biology 2025-10-03 Ekaterina Podplutova , Anastasia Vepreva , Olga A. Konovalova , Vladimir Vinogradov , Dmitrii O. Shkil , Andrei Dmitrenko

Generating molecules with desired biological activities has attracted growing attention in drug discovery. Previous molecular generation models are designed as chemocentric methods that hardly consider the drug-target interaction, limiting…

Machine Learning · Computer Science 2022-10-24 Cheng Tan , Zhangyang Gao , Stan Z. Li

The rational design of novel molecules with desired bioactivity is a critical but challenging task in drug discovery, especially when treating a novel target family or understudied targets. Here, we propose PGMG, a pharmacophore-guided deep…

Biomolecules · Quantitative Biology 2022-07-05 Huimin Zhu , Renyi Zhou , Jing Tang , Min Li

Generative Flow Networks, or GFlowNets, offer a promising framework for molecular design, but their internal decision policies remain opaque. This limits adoption in drug discovery, where chemists require clear and interpretable rationales…

Machine Learning · Computer Science 2025-11-25 Amirtha Varshini A S , Duminda S. Ranasinghe , Hok Hei Tam

Machine learning in drug discovery has been focused on virtual screening of molecular libraries using discriminative models. Generative models are an entirely different approach that learn to represent and optimize molecules in a continuous…

Quantitative Methods · Quantitative Biology 2020-11-17 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

Since its foundations, more than one hundred years ago, the field of structural biology has strived to understand and analyze the properties of molecules and their interactions by studying the structure that they take in 3D space. However,…

Biomolecules · Quantitative Biology 2023-02-27 Gabriele Corso