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Generating molecules that satisfy precise numeric constraints over multiple physicochemical properties is critical and challenging. Although large language models (LLMs) are expressive, they struggle with precise multi-objective control and…

Artificial Intelligence · Computer Science 2026-01-19 Yizhan Li , Florence Cloutier , Sifan Wu , Ali Parviz , Boris Knyazev , Yan Zhang , Glen Berseth , Bang Liu

Recently, molecule generation using deep learning has been actively investigated in drug discovery. In this field, Transformer and VAE are widely used as powerful models, but they are rarely used in combination due to structural and…

Biomolecules · Quantitative Biology 2024-04-08 Yasuhiro Yoshikai , Tadahaya Mizuno , Shumpei Nemoto , Hiroyuki Kusuhara

Recent advances in diffusion models have shown remarkable potential in the conditional generation of novel molecules. These models can be guided in two ways: (i) explicitly, through additional features representing the condition, or (ii)…

Machine Learning · Computer Science 2025-03-12 Yuchen Shen , Chenhao Zhang , Sijie Fu , Chenghui Zhou , Newell Washburn , Barnabás Póczos

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

Generative molecular optimization aims to design molecules with properties surpassing those of existing compounds. However, such candidates are rare and expensive to evaluate, yielding sample efficiency essential. Additionally, surrogate…

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

Designing a single molecule that modulates two targets is a promising strategy for polypharmacology, but it remains substantially harder than standard single-target generation because one candidate must satisfy two binding requirements…

Machine Learning · Computer Science 2026-05-26 Qingyuan Zeng , Pengxiang Cai , Zixin Guan , Ziyang Chen , Anglin Liu , Lang Qin , Xinyao Lai , Jintai Chen

Generative AI has redefined artificial intelligence, enabling the creation of innovative content and customized solutions that drive business practices into a new era of efficiency and creativity. In this paper, we focus on diffusion…

Machine Learning · Computer Science 2024-03-21 Zihao Li , Hui Yuan , Kaixuan Huang , Chengzhuo Ni , Yinyu Ye , Minshuo Chen , Mengdi Wang

Generating molecular graphs is a challenging task due to their discrete nature and the competitive objectives involved. Diffusion models have emerged as SOTA approaches in data generation across various modalities. For molecular graphs,…

Machine Learning · Computer Science 2025-01-08 Prashanth Pombala , Gerrit Grossmann , Verena Wolf

In recent years the scientific community has devoted much effort in the development of deep learning models for the generation of new molecules with desirable properties (i.e. drugs). This has produced many proposals in literature. However,…

Machine Learning · Computer Science 2020-08-24 Davide Rigoni , Nicolò Navarin , Alessandro Sperduti

Traditional drug discovery programs are being transformed by the advent of machine learning methods. Among these, Generative AI methods (GM) have gained attention due to their ability to design new molecules and enhance specific properties…

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

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

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

The paradigm shift toward structure-driven molecule generation has been propelled by advances in deep generative models, such as variational auto-encoders and diffusion models. However, these generative models for molecular design remain…

Machine Learning · Computer Science 2026-04-17 Peidong Liu , Wenbo Zhang , Wei Ju , Jiancheng Lv , Xianggen Liu

Achieving precise control over a molecule's biological activity-encompassing targeted activation/inhibition, cooperative multi-target modulation, and off-target toxicity mitigation-remains a critical challenge in de novo drug design.…

Machine Learning · Computer Science 2025-08-11 Renyi Zhou , Huimin Zhu , Jing Tang , Min Li

n this work, we propose a latent molecular diffusion model that can make the generated 3D molecules rich in diversity and maintain rich geometric features. The model captures the information of the forces and local constraints between atoms…

Machine Learning · Computer Science 2024-12-06 Xiang Chen

Protein design with desirable properties has been a significant challenge for many decades. Generative artificial intelligence is a promising approach and has achieved great success in various protein generation tasks. Notably, diffusion…

A novel framework has recently been proposed for designing the molecular structure of chemical compounds with a desired chemical property, where design of novel drugs is an important topic in bioinformatics and chemo-informatics. The…

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