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Recently, utilizing reinforcement learning (RL) to generate molecules with desired properties has been highlighted as a promising strategy for drug design. A molecular docking program - a physical simulation that estimates protein-small…

Quantitative Methods · Quantitative Biology 2021-10-28 Soojung Yang , Doyeong Hwang , Seul Lee , Seongok Ryu , Sung Ju Hwang

Developing new drugs is laborious and costly, demanding extensive time investment. In this paper, we introduce a de-novo drug design strategy, which harnesses the capabilities of language models to devise targeted drugs for specific…

Biomolecules · Quantitative Biology 2025-05-20 Salma J. Ahmed , Emad A. Mohammed

Machine learning has the potential to automate molecular design and drastically accelerate the discovery of new functional compounds. Towards this goal, generative models and reinforcement learning (RL) using string and graph…

Machine Learning · Computer Science 2022-02-02 Daniel Flam-Shepherd , Alexander Zhigalin , Alán Aspuru-Guzik

De novo molecular design has facilitated the exploration of large chemical space to accelerate drug discovery. Structure-based de novo method can overcome the data scarcity of active ligands by incorporating drug-target interaction into…

Biomolecules · Quantitative Biology 2022-09-16 Yaqin Li , Lingli Li , Yongjin Xu , Yi Yu

Generating molecules with desired chemical properties presents a critical challenge in fields such as chemical synthesis and drug discovery. Recent advancements in artificial intelligence (AI) and deep learning have significantly…

Machine Learning · Computer Science 2025-09-25 Chen Li , Huidong Tang , Ye Zhu , Yoshihiro Yamanishi

Automating molecular design using deep reinforcement learning (RL) holds the promise of accelerating the discovery of new chemical compounds. Existing approaches work with molecular graphs and thus ignore the location of atoms in space,…

Machine Learning · Statistics 2021-03-02 Gregor N. C. Simm , Robert Pinsler , José Miguel Hernández-Lobato

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

Reinforcement learning (RL) over text representations can be effective for finding high-value policies that can search over graphs. However, RL requires careful structuring of the search space and algorithm design to be effective in this…

Machine Learning · Computer Science 2023-10-05 Raj Ghugare , Santiago Miret , Adriana Hugessen , Mariano Phielipp , Glen Berseth

Fine-tuning foundation models has emerged as a powerful approach for generating objects with specific desired properties. Reinforcement learning (RL) provides an effective framework for this purpose, enabling models to generate outputs that…

Machine Learning · Computer Science 2025-11-04 Pouya M. Ghari , Simone Sciabola , Ye Wang

Efficient design and discovery of target-driven molecules is a critical step in facilitating lead optimization in drug discovery. Current approaches to develop molecules for a target protein are intuition-driven, hampered by slow iterative…

Machine Learning · Computer Science 2022-05-24 Andrew D. McNaughton , Mridula S. Bontha , Carter R. Knutson , Jenna A. Pope , Neeraj Kumar

Generative models have made significant progress in synthesizing visual content, including images, videos, and 3D/4D structures. However, they are typically trained with surrogate objectives such as likelihood or reconstruction loss, which…

Computer Vision and Pattern Recognition · Computer Science 2026-01-21 Yuanzhi Liang , Yijie Fang , Ke Hao , Rui Li , Ziqi Ni , Ruijie Su , Chi Zhang

Current generative models for drug discovery primarily use molecular docking as an oracle to guide the generation of active compounds. However, such models are often not useful in practice because even compounds with high docking scores do…

Machine Learning · Computer Science 2025-06-11 Peter Eckmann , Dongxia Wu , Germano Heinzelmann , Michael K. Gilson , Rose Yu

Protein sequence design, determined by amino acid sequences, are essential to protein engineering problems in drug discovery. Prior approaches have resorted to evolutionary strategies or Monte-Carlo methods for protein design, but often…

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we…

Designing de novo 3D molecules with desirable properties remains a fundamental challenge in drug discovery and molecular engineering. While diffusion models have demonstrated remarkable capabilities in generating high-quality 3D molecular…

Machine Learning · Computer Science 2026-01-15 Lianghong Chen , Dongkyu Eugene Kim , Mike Domaratzki , Pingzhao Hu

Reinforcement learning (RL) is a powerful approach to enhance task-oriented dialogue (TOD) systems. However, existing RL methods tend to mainly focus on generation tasks, such as dialogue policy learning (DPL) or response generation (RG),…

Artificial Intelligence · Computer Science 2024-06-21 Huifang Du , Shuqin Li , Minghao Wu , Xuejing Feng , Yuan-Fang Li , Haofen Wang

Decoding-based regression, which reformulates regression as a sequence generation task, has emerged as a promising paradigm of applying large language models for numerical prediction. However, its progress is hindered by the misalignment…

Machine Learning · Computer Science 2025-12-09 Ming Chen , Sheng Tang , Rong-Xi Tan , Ziniu Li , Jiacheng Chen , Ke Xue , Chao Qian

Program synthesis or code generation aims to generate a program that satisfies a problem specification. Recent approaches using large-scale pretrained language models (LMs) have shown promising results, yet they have some critical…

Machine Learning · Computer Science 2022-11-04 Hung Le , Yue Wang , Akhilesh Deepak Gotmare , Silvio Savarese , Steven C. H. Hoi

Reinforcement learning (RL) has been widely used in training large language models (LLMs) for preventing unexpected outputs, eg reducing harmfulness and errors. However, existing RL methods mostly adopt the instance-level reward, which is…

Computation and Language · Computer Science 2024-06-18 Zhipeng Chen , Kun Zhou , Wayne Xin Zhao , Junchen Wan , Fuzheng Zhang , Di Zhang , Ji-Rong Wen

Diffusion models excel at modeling complex data distributions, including those of images, proteins, and small molecules. However, in many cases, our goal is to model parts of the distribution that maximize certain properties: for example,…

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