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Related papers: Geometric-informed GFlowNets for Structure-Based D…

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Several generative models with elaborate training and sampling procedures have been proposed to accelerate structure-based drug design (SBDD); however, their empirical performance turns out to be suboptimal. We seek to better understand…

Machine Learning · Computer Science 2025-03-04 Rafał Karczewski , Samuel Kaski , Markus Heinonen , Vikas Garg

Sampling useful three-dimensional molecular structures along with their most favorable conformations is a key challenge in drug discovery. Current state-of-the-art 3D de-novo design flow matching or diffusion-based models are limited to…

Machine Learning · Computer Science 2025-11-24 Riccardo Tedoldi , Ola Engkvist , Patrick Bryant , Hossein Azizpour , Jon Paul Janet , Alessandro Tibo

Generative Flow Networks (GFlowNets), a new family of probabilistic samplers, have recently emerged as a promising framework for learning stochastic policies that generate high-quality and diverse objects proportionally to their rewards.…

Machine Learning · Computer Science 2024-06-05 Chunhui Li , Cheng-Hao Liu , Dianbo Liu , Qingpeng Cai , Ling Pan

Generative flow networks (GFlowNets) are a family of algorithms that learn a generative policy to sample discrete objects $x$ with non-negative reward $R(x)$. Learning objectives guarantee the GFlowNet samples $x$ from the target…

Machine Learning · Computer Science 2023-05-15 Max W. Shen , Emmanuel Bengio , Ehsan Hajiramezanali , Andreas Loukas , Kyunghyun Cho , Tommaso Biancalani

Generative Flow Networks (GFlowNets) have been introduced as a method to sample a diverse set of candidates in an active learning context, with a training objective that makes them approximately sample in proportion to a given reward…

Machine Learning · Computer Science 2026-01-27 Yoshua Bengio , Salem Lahlou , Tristan Deleu , Edward J. Hu , Mo Tiwari , Emmanuel Bengio

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

Deep generative models such as flow and diffusion models have proven to be effective in modeling high-dimensional and complex data types such as videos or proteins, and this has motivated their use in different data modalities, such as…

Machine Learning · Computer Science 2025-04-08 Ege Erdogan

Motivation: Structure-based drug design (SBDD) has advanced with deep generative models, but bridging the gap between continuous atomic coordinates and discrete atom types remains a challenge. Current approaches, such as diffusion and flow…

Geometric Graph Neural Networks (GNNs) and Transformers have become state-of-the-art for learning from 3D protein structures. However, their reliance on message passing prevents them from capturing the hierarchical interactions that govern…

Machine Learning · Computer Science 2025-12-09 Chang Liu , Vivian Li , Linus Leong , Vladimir Radenkovic , Pietro Liò , Chaitanya K. Joshi

Chemical space exploration underlies drug discovery, yet most generative models treat chemical space as a fixed, implicitly learned distribution, focusing on sampling molecules rather than deliberately designing the space itself. We…

The process of screening molecules for desirable properties is a key step in several applications, ranging from drug discovery to material design. During the process of drug discovery specifically, protein-ligand docking, or chemical…

Machine Learning · Computer Science 2022-11-08 Ryien Hosseini , Filippo Simini , Austin Clyde , Arvind Ramanathan

Graph neural networks (GNNs) have been used extensively for addressing problems in drug design and discovery. Both ligand and target molecules are represented as graphs with node and edge features encoding information about atomic elements…

Machine Learning · Computer Science 2021-10-14 Dhananjay Bhaskar , Jackson D. Grady , Michael A. Perlmutter , Smita Krishnaswamy

Generative models hold great promise for small molecule discovery, significantly increasing the size of search space compared to traditional in silico screening libraries. However, most existing machine learning methods for small molecule…

Fragment-based drug design is a promising strategy leveraging the binding of small chemical moieties that can efficiently guide drug discovery. The initial step of fragment identification remains challenging, as fragments often bind weakly…

Biomolecules · Quantitative Biology 2025-09-17 Rebecca Manuela Neeser , Ilia Igashov , Arne Schneuing , Michael Bronstein , Philippe Schwaller , Bruno Correia

Nowadays there is a big spotlight cast on the development of techniques of explainable machine learning. Here we introduce a new computational paradigm based on Group Equivariant Non-Expansive Operators, that can be regarded as the product…

Predicting the binding sites of target proteins plays a fundamental role in drug discovery. Most existing deep-learning methods consider a protein as a 3D image by spatially clustering its atoms into voxels and then feed the voxelized…

Biomolecules · Quantitative Biology 2024-07-24 Yang Zhang , Zhewei Wei , Ye Yuan , Chongxuan Li , Wenbing Huang

Geometric deep learning has recently achieved great success in non-Euclidean domains, and learning on 3D structures of large biomolecules is emerging as a distinct research area. However, its efficacy is largely constrained due to the…

Machine Learning · Computer Science 2023-10-31 Fang Wu , Lirong Wu , Dragomir Radev , Jinbo Xu , Stan Z. Li

Diffusion generative models have emerged as a powerful framework for addressing problems in structural biology and structure-based drug design. These models operate directly on 3D molecular structures. Due to the unfavorable scaling of…

Biomolecules · Quantitative Biology 2024-05-10 Ian Dunn , David Ryan Koes

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

GFlowNets are a promising alternative to MCMC sampling for discrete compositional random variables. Training GFlowNets requires repeated evaluations of the unnormalized target distribution or reward function. However, for large-scale…

Machine Learning · Computer Science 2024-06-06 Tiago da Silva , Luiz Max Carvalho , Amauri Souza , Samuel Kaski , Diego Mesquita