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The goal of structure-based drug discovery is to find small molecules that bind to a given target protein. Deep learning has been used to generate drug-like molecules with certain cheminformatic properties, but has not yet been applied to…

Quantitative Methods · Quantitative Biology 2022-01-27 Matthew Ragoza , Tomohide Masuda , David Ryan Koes

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

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…

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

A fundamental problem in drug discovery is to design molecules that bind to specific proteins. To tackle this problem using machine learning methods, here we propose a novel and effective framework, known as GraphBP, to generate 3D…

Biomolecules · Quantitative Biology 2022-05-31 Meng Liu , Youzhi Luo , Kanji Uchino , Koji Maruhashi , Shuiwang Ji

Designing molecules that bind to specific target proteins is a fundamental task in drug discovery. Recent models leverage geometric constraints to generate ligand molecules that bind cohesively with specific protein pockets. However, these…

Biomolecules · Quantitative Biology 2023-04-26 Fang Sun , Zhihao Zhan , Hongyu Guo , Ming Zhang , Jian Tang

With the recent advances in machine learning for quantum chemistry, it is now possible to predict the chemical properties of compounds and to generate novel molecules. Existing generative models mostly use a string- or graph-based…

Biomolecules · Quantitative Biology 2020-10-14 Vitali Nesterov , Mario Wieser , Volker Roth

Cryo-EM reconstruction algorithms seek to determine a molecule's 3D density map from a series of noisy, unlabeled 2D projection images captured with an electron microscope. Although reconstruction algorithms typically model the 3D volume as…

Biomolecules · Quantitative Biology 2021-07-06 Ellen D. Zhong , Adam Lerer , Joseph H. Davis , Bonnie Berger

Graph neural networks are emerging as promising methods for modeling molecular graphs, in which nodes and edges correspond to atoms and chemical bonds, respectively. Recent studies show that when 3D molecular geometries, such as bond…

Machine Learning · Computer Science 2021-10-06 Zhao Xu , Youzhi Luo , Xuan Zhang , Xinyi Xu , Yaochen Xie , Meng Liu , Kaleb Dickerson , Cheng Deng , Maho Nakata , Shuiwang Ji

Molecule generation is a challenging open problem in cheminformatics. Currently, deep generative approaches addressing the challenge belong to two broad categories, differing in how molecules are represented. One approach encodes molecular…

Machine Learning · Statistics 2020-11-02 Marco Podda , Davide Bacciu , Alessio Micheli

We propose a new score-based approach to generate 3D molecules represented as atomic densities on regular grids. First, we train a denoising neural network that learns to map from a smooth distribution of noisy molecules to the distribution…

Deep generative models for structure-based drug design (SBDD), where molecule generation is conditioned on a 3D protein pocket, have received considerable interest in recent years. These methods offer the promise of higher-quality molecule…

Biomolecules · Quantitative Biology 2023-08-16 Charles Harris , Kieran Didi , Arian R. Jamasb , Chaitanya K. Joshi , Simon V. Mathis , Pietro Lio , Tom Blundell

Structure-based drug design aims at generating high affinity ligands with prior knowledge of 3D target structures. Existing methods either use conditional generative model to learn the distribution of 3D ligands given target binding sites,…

Biomolecules · Quantitative Biology 2024-03-18 Yuwei Yang , Siqi Ouyang , Xueyu Hu , Mingyue Zheng , Hao Zhou , Lei Li

In the field of computational molecule generation, an essential task in the discovery of new chemical compounds, fragment-based deep generative models are a leading approach, consistently achieving state-of-the-art results in molecular…

Biomolecules · Quantitative Biology 2024-05-10 Sergei Voloboev

Generative models of 3D molecular structure play a rapidly growing role in the design and simulation of molecules. Diffusion models currently dominate the space of 3D molecule generation, while autoregressive models have trailed behind. In…

Machine Learning · Computer Science 2025-09-10 Austin H. Cheng , Chong Sun , Alán Aspuru-Guzik

Recent methods for molecular generation face a trade-off: they either enforce strict equivariance with costly architectures or relax it to gain scalability and flexibility. We propose a frame-based diffusion paradigm that achieves…

Machine Learning · Computer Science 2025-10-07 Mohan Guo , Cong Liu , Patrick Forré

Graph generation techniques are increasingly being adopted for drug discovery. Previous graph generation approaches have utilized relatively small molecular building blocks such as atoms or simple cycles, limiting their effectiveness to…

Machine Learning · Computer Science 2020-04-21 Wengong Jin , Regina Barzilay , Tommi Jaakkola

Molecular dynamics (MD) is a crucial technique for simulating biological systems, enabling the exploration of their dynamic nature and fostering an understanding of their functions and properties. To address exploration inefficiency,…

Quantitative Methods · Quantitative Biology 2024-05-03 Shaoning Li , Yusong Wang , Mingyu Li , Jian Zhang , Bin Shao , Nanning Zheng , Jian Tang

Proteins in complex with small molecule ligands represent the core of structure-based drug discovery. However, three-dimensional representations are absent from most deep-learning-based generative models. We here present a graph-based…

Biomolecules · Quantitative Biology 2022-04-07 Seung-gu Kang , Jeffrey K. Weber , Joseph A. Morrone , Leili Zhang , Tien Huynh , Wendy D. Cornell

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