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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

Finetuning a Large Language Model (LLM) is crucial for generating results towards specific objectives. This research delves into the realm of drug optimization and introduce a novel reinforcement learning algorithm to finetune a drug…

Machine Learning · Computer Science 2025-02-12 Xuefeng Liu , Songhao Jiang , Siyu Chen , Zhuoran Yang , Yuxin Chen , Ian Foster , Rick Stevens

Deep learning-based approaches for generating novel drug molecules with specific properties have gained a lot of interest in the last few years. Recent studies have demonstrated promising performance for string-based generation of novel…

Biomolecules · Quantitative Biology 2025-02-18 Hampus Gummesson Svensson , Christian Tyrchan , Ola Engkvist , Morteza Haghir Chehreghani

A rational design of new therapeutic drugs aims to find a molecular structure with desired biological functionality, e.g., an ability to activate or suppress a specific protein via binding to it. Molecular docking is a common technique for…

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

De novo drug design is a crucial component of modern drug development, yet navigating the vast chemical space to find synthetically accessible, high-affinity candidates remains a significant challenge. Reinforcement Learning (RL) enhances…

Machine Learning · Computer Science 2025-12-25 R Yadunandan , Nimisha Ghosh

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…

De novo drug design is a pivotal issue in pharmacology and a new area of focus in AI for science research. A central challenge in this field is to generate molecules with specific properties while also producing a wide range of diverse…

Biomolecules · Quantitative Biology 2024-01-15 Xiuyuan Hu , Guoqing Liu , Yang Zhao , Hao Zhang

Chemical language models, combined with reinforcement learning (RL), have shown significant promise to efficiently traverse large chemical spaces for drug discovery. However, the performance of various RL algorithms and their best practices…

Machine Learning · Computer Science 2025-11-06 Morgan Thomas , Albert Bou , Jose Carlos Gómez-Tamayo , Gary Tresadern , Mazen Ahmad , Gianni De Fabritiis

Motivation: The development of novel compounds targeting proteins of interest is one of the most important tasks in the pharmaceutical industry. Deep generative models have been applied to targeted molecular design and have shown promising…

Machine Learning · Computer Science 2022-09-05 Gökçe Uludoğan , Elif Ozkirimli , Kutlu O. Ulgen , Nilgün Karalı , Arzucan Özgür

This study investigates the effectiveness of reinforcement learning (RL) fine-tuning techniques on a compact language model (Qwen2.5-0.5B Base) for two challenging tasks: instruction following and mathematical reasoning. We compare…

Computation and Language · Computer Science 2025-07-29 Yifu Han , Geo Zhang

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

Reinforcement learning (RL) is a powerful machine learning technique that enables an intelligent agent to learn an optimal policy that maximizes the cumulative rewards in sequential decision making. Most of methods in the existing…

Machine Learning · Statistics 2023-01-06 Chengchun Shi , Zhengling Qi , Jianing Wang , Fan Zhou

Reinforcement learning (RL) has emerged as a powerful paradigm for fine-tuning Large Language Models (LLMs) for text generation. In particular, recent LLMs such as ChatGPT and GPT-4 can engage in fluent conversations with users after…

Machine Learning · Computer Science 2023-11-14 Jonathan D. Chang , Kiante Brantley , Rajkumar Ramamurthy , Dipendra Misra , Wen Sun

Fine-tuning a pre-trained generative model has demonstrated good performance in generating promising drug molecules. The fine-tuning task is often formulated as a reinforcement learning problem, where previous methods efficiently learn to…

Machine Learning · Computer Science 2025-11-12 Hampus Gummesson Svensson , Christian Tyrchan , Ola Engkvist , Morteza Haghir Chehreghani

Large Language Models (LLMs) have the potential to accelerate small molecule drug design due to their ability to reason about information from diverse sources and formats. However, their practical utility remains unclear due to the lack of…

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

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

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

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
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