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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

Molecular conformation generation (MCG) is a fundamental and important problem in drug discovery. Many traditional methods have been developed to solve the MCG problem, such as systematic searching, model-building, random searching,…

Computational Engineering, Finance, and Science · Computer Science 2023-03-28 Gengmo Zhou , Zhifeng Gao , Zhewei Wei , Hang Zheng , Guolin Ke

We present a new approach, the Topograph, which reconstructs underlying physics processes, including the intermediary particles, by leveraging underlying priors from the nature of particle physics decays and the flexibility of message…

High Energy Physics - Phenomenology · Physics 2023-10-16 Lukas Ehrke , John Andrew Raine , Knut Zoch , Manuel Guth , Tobias Golling

Although machine learning has been successfully used to propose novel molecules that satisfy desired properties, it is still challenging to explore a large chemical space efficiently. In this paper, we present a conditional molecular design…

Machine Learning · Computer Science 2019-04-02 Seokho Kang , Kyunghyun Cho

Discovering new drug molecules is a pivotal yet challenging process due to the near-infinitely large chemical space and notorious demands on time and resources. Numerous generative models have recently been introduced to accelerate the drug…

Computational Engineering, Finance, and Science · Computer Science 2025-12-23 Shitong Luo , Wenhao Gao , Zuofan Wu , Jian Peng , Connor W. Coley , Jianzhu Ma

Molecular property calculations are the bedrock of chemical physics. High-fidelity \textit{ab initio} modeling techniques for computing the molecular properties can be prohibitively expensive, and motivate the development of…

Machine Learning · Computer Science 2022-11-28 Hatem Helal , Jesun Firoz , Jenna Bilbrey , Mario Michael Krell , Tom Murray , Ang Li , Sotiris Xantheas , Sutanay Choudhury

We propose Composition Sampling, a simple but effective method to generate diverse outputs for conditional generation of higher quality compared to previous stochastic decoding strategies. It builds on recently proposed plan-based neural…

Computation and Language · Computer Science 2022-03-30 Shashi Narayan , Gonçalo Simões , Yao Zhao , Joshua Maynez , Dipanjan Das , Michael Collins , Mirella Lapata

Generative models have achieved impressive results in many domains including image and text generation. In the natural sciences, generative models have led to rapid progress in automated drug discovery. Many of the current methods focus on…

Machine Learning · Computer Science 2019-09-04 Jordan Hoffmann , Louis Maestrati , Yoshihide Sawada , Jian Tang , Jean Michel Sellier , Yoshua Bengio

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

Molecular generation and molecular property prediction are both crucial for drug discovery, but they are often developed independently. Inspired by recent studies, which demonstrate that diffusion model, a prominent generative approach, can…

Machine Learning · Computer Science 2025-04-07 Shikun Feng , Yuyan Ni , Yan Lu , Zhi-Ming Ma , Wei-Ying Ma , Yanyan Lan

This work introduces a method to tune a sequence-based generative model for molecular de novo design that through augmented episodic likelihood can learn to generate structures with certain specified desirable properties. We demonstrate how…

Artificial Intelligence · Computer Science 2017-08-30 Marcus Olivecrona , Thomas Blaschke , Ola Engkvist , Hongming Chen

We view molecular optimization as a graph-to-graph translation problem. The goal is to learn to map from one molecular graph to another with better properties based on an available corpus of paired molecules. Since molecules can be…

Machine Learning · Computer Science 2019-01-30 Wengong Jin , Kevin Yang , Regina Barzilay , Tommi Jaakkola

This paper proposes a machine learning (ML) method to predict stable molecular geometries from their chemical composition. The method is useful for generating molecular conformations which may serve as initial geometries for saving time…

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

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the…

Machine Learning · Statistics 2016-08-26 Steven Kearnes , Kevin McCloskey , Marc Berndl , Vijay Pande , Patrick Riley

When designing new molecules with particular properties, it is not only important what to make but crucially how to make it. These instructions form a synthesis directed acyclic graph (DAG), describing how a large vocabulary of simple…

Machine Learning · Computer Science 2020-12-22 John Bradshaw , Brooks Paige , Matt J. Kusner , Marwin H. S. Segler , José Miguel Hernández-Lobato

The de novo design of molecular structures using deep learning generative models introduces an encouraging solution to drug discovery in the face of the continuously increased cost of new drug development. From the generation of original…

Biomolecules · Quantitative Biology 2021-02-08 Yuemin Bian , Xiang-Qun Xie

One of the major applications of generative models for drug Discovery targets the lead-optimization phase. During the optimization of a lead series, it is common to have scaffold constraints imposed on the structure of the molecules…

Quantitative Methods · Quantitative Biology 2021-01-05 Maxime Langevin , Herve Minoux , Maximilien Levesque , Marc Bianciotto

We seek to automate the design of molecules based on specific chemical properties. In computational terms, this task involves continuous embedding and generation of molecular graphs. Our primary contribution is the direct realization of…

Machine Learning · Computer Science 2019-04-01 Wengong Jin , Regina Barzilay , Tommi Jaakkola

Molecular machine learning has gained popularity with the advancements of geometric deep learning. In parallel, retrieval-augmented generation has become a principled approach commonly used with language models. However, the optimal…

Machine Learning · Computer Science 2025-07-04 Runzhong Wang , Rui-Xi Wang , Mrunali Manjrekar , Connor W. Coley
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