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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…

Retrosynthesis planning remains a central challenge in molecular discovery due to the vast and complex chemical reaction space. While traditional template-based methods offer tractability, they suffer from poor scalability and limited…

Machine Learning · Computer Science 2025-07-31 Nguyen Xuan-Vu , Daniel P Armstrong , Zlatko Jončev , Philippe Schwaller

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…

In this work, we introduce a method to fine-tune a Transformer-based generative model for molecular de novo design. Leveraging the superior sequence learning capacity of Transformers over Recurrent Neural Networks (RNNs), our model can…

Machine Learning · Computer Science 2024-03-11 Pengcheng Xu , Tao Feng , Tianfan Fu , Siddhartha Laghuvarapu , Jimeng Sun

Synthesizability in small molecule generative design remains a bottleneck. Existing works that do consider synthesizability can output predicted synthesis routes for generated molecules. However, there has been minimal attention in…

Biomolecules · Quantitative Biology 2025-05-14 Jeff Guo , Víctor Sabanza-Gil , Zlatko Jončev , Jeremy S. Luterbacher , Philippe Schwaller

The challenge of discovering new molecules with desired properties is crucial in domains like drug discovery and material design. Recent advances in deep learning-based generative methods have shown promise but face the issue of sample…

Biomolecules · Quantitative Biology 2024-12-31 Hyeonah Kim , Minsu Kim , Sanghyeok Choi , Jinkyoo Park

The application of generative models for experimental drug discovery campaigns is severely limited by the difficulty of designing molecules de novo that can be synthesized in practice. Previous works have leveraged Generative Flow Networks…

Generative Flow Networks (GFlowNets) learn to sample diverse candidates in proportion to a reward function, making them well-suited for scientific discovery, where exploring multiple promising solutions is crucial. Further extending…

Machine Learning · Computer Science 2026-05-29 Seokwon Yoon , Youngbin Choi , Seunghyuk Cho , Seungbeom Lee , MoonJeong Park , Dongwoo Kim

Generative Flow Networks (GFlowNets), a class of generative models have recently emerged as a suitable framework for generating diverse and high-quality molecular structures by learning from unnormalized reward distributions. Previous works…

Machine Learning · Computer Science 2024-09-17 Mohit Pandey , Gopeshh Subbaraj , Emmanuel Bengio

The discovery of functional molecules is an expensive and time-consuming process, exemplified by the rising costs of small molecule therapeutic discovery. One class of techniques of growing interest for early-stage drug discovery is de novo…

Quantitative Methods · Quantitative Biology 2020-02-18 Wenhao Gao , Connor W. Coley

Deep generative models that produce novel molecular structures have the potential to facilitate chemical discovery. Flow matching is a recently proposed generative modeling framework that has achieved impressive performance on a variety of…

Machine Learning · Computer Science 2024-11-26 Ian Dunn , David R. Koes

High-content phenotypic screening, including high-content imaging (HCI), has gained popularity in the last few years for its ability to characterize novel therapeutics without prior knowledge of the protein target. When combined with deep…

Recent work has proposed a promising approach to improving scalability of program synthesis by allowing the user to supply a syntactic template that constrains the space of potential programs. Unfortunately, creating templates often…

Programming Languages · Computer Science 2017-04-18 Jeevana Priya Inala , Nadia Polikarpova , Xiaokang Qiu , Benjamin S. Lerner , Armando Solar-Lezama

Generating new molecules with specified chemical and biological properties via generative models has emerged as a promising direction for drug discovery. However, existing methods require extensive training/fine-tuning with a large dataset,…

Quantitative Methods · Quantitative Biology 2023-04-25 Zichao Wang , Weili Nie , Zhuoran Qiao , Chaowei Xiao , Richard Baraniuk , Anima Anandkumar

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

De novo 3D molecule generation is a pivotal task in drug discovery. However, many recent geometric generative models struggle to produce high-quality 3D structures, even if they maintain 2D validity and topological stability. To tackle this…

Machine Learning · Computer Science 2025-05-27 Danny Reidenbach , Filipp Nikitin , Olexandr Isayev , Saee Paliwal

This paper is about the problem of learning a stochastic policy for generating an object (like a molecular graph) from a sequence of actions, such that the probability of generating an object is proportional to a given positive reward for…

Machine Learning · Computer Science 2021-11-22 Emmanuel Bengio , Moksh Jain , Maksym Korablyov , Doina Precup , Yoshua Bengio

A generative model capable of sampling realistic molecules with desired properties could accelerate chemical discovery across a wide range of applications. Toward this goal, significant effort has focused on developing models that jointly…

Machine Learning · Computer Science 2025-08-19 Ian Dunn , David R. Koes

Synthesizability in generative molecular design remains a pressing challenge. Existing methods to assess synthesizability span heuristics-based methods, retrosynthesis models, and synthesizability-constrained molecular generation. The…

Biomolecules · Quantitative Biology 2024-07-18 Jeff Guo , Philippe Schwaller

Generative Flow Networks (GFlowNets) have recently emerged as a suitable framework for generating diverse and high-quality molecular structures by learning from rewards treated as unnormalized distributions. Previous works in this framework…

Machine Learning · Computer Science 2025-06-13 Mohit Pandey , Gopeshh Subbaraj , Artem Cherkasov , Martin Ester , Emmanuel Bengio
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