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Large Language models (LLMs) have emerged as powerful tools for addressing challenges across diverse domains. Notably, recent studies have demonstrated that large language models significantly enhance the efficiency of biomolecular analysis…

Computation and Language · Computer Science 2025-03-07 Jiyue Jiang , Zikang Wang , Yuheng Shan , Heyan Chai , Jiayi Li , Zixian Ma , Xinrui Zhang , Yu Li

Protein-ligand scoring is a central component of structure-based drug design, underpinning molecular docking, virtual screening, and pose optimization. Conventional physics-based energy functions are often computationally expensive,…

Biomolecules · Quantitative Biology 2026-02-24 Zhangfan Yang , Baoyun Chen , Dong Xu , Jia Wang , Ruibin Bai , Junkai Ji , Zexuan Zhu

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as…

Structure-based drug design (SBDD) is crucial for developing specific and effective therapeutics against protein targets but remains challenging due to complex protein-ligand interactions and vast chemical space. Although language models…

Biomolecules · Quantitative Biology 2024-08-20 Cong Fu , Xiner Li , Blake Olson , Heng Ji , Shuiwang Ji

Virtual Screening is an essential technique in the early phases of drug discovery, aimed at identifying promising drug candidates from vast molecular libraries. Recently, ligand-based virtual screening has garnered significant attention due…

Biomolecules · Quantitative Biology 2024-11-22 Gengmo Zhou , Zhen Wang , Feng Yu , Guolin Ke , Zhewei Wei , Zhifeng Gao

The identification of novel drug-target (DT) interactions is a substantial part of the drug discovery process. Most of the computational methods that have been proposed to predict DT interactions have focused on binary classification, where…

Machine Learning · Statistics 2019-02-06 Hakime Öztürk , Elif Ozkirimli , Arzucan Özgür

Currently, the field of structure-based drug design is dominated by three main types of algorithms: search-based algorithms, deep generative models, and reinforcement learning. While existing works have typically focused on comparing models…

Machine Learning · Computer Science 2026-01-22 Kangyu Zheng , Kai Zhang , Jiale Tan , Xuehan Chen , Yingzhou Lu , Zaixi Zhang , Lichao Sun , Marinka Zitnik , Tianfan Fu , Zhiding Liang

Accurate prediction of protein-ligand binding affinity remains a central challenge in structure-based drug discovery. The effectiveness of machine learning models critically depends on the quality of molecular descriptors, for which…

Biomolecules · Quantitative Biology 2026-03-24 Jian Liu , Hongsong Feng

The de novo design of ligand-binding proteins with tailored functions is essential for advancing biotechnology and molecular medicine, yet existing AI approaches are limited by scarce protein-ligand complex data. To circumvent this data…

Machine Learning · Computer Science 2026-03-03 Zhenqiao Song , Ramith Hettiarachchi , Chuan Li , Jianwen Xie , Lei Li

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

Machine Learning · Computer Science 2024-07-17 Seungyeon Choi , Sangmin Seo , Sanghyun Park

Molecular Relational Learning (MRL) aims to understand interactions between molecular pairs, playing a critical role in advancing biochemical research. With the recent development of large language models (LLMs), a growing number of studies…

Machine Learning · Computer Science 2025-06-03 Zhuo Chen , Yizhen Zheng , Huan Yee Koh , Hongxin Xiang , Linjiang Chen , Wenjie Du , Yang Wang

Is it feasible to create an analysis paradigm that can analyze and then accurately and quickly predict known drugs from experimental data? PharML.Bind is a machine learning toolkit which is able to accomplish this feat. Utilizing deep…

Biomolecules · Quantitative Biology 2019-11-15 Aaron D. Vose , Jacob Balma , Damon Farnsworth , Kaylie Anderson , Yuri K. Peterson

In the real world, a molecule is a 3D geometric structure. Compared to 1D SMILES sequences and 2D molecular graphs, 3D molecules represent the most informative molecular modality. Despite the rapid progress of autoregressive-based language…

Computational Engineering, Finance, and Science · Computer Science 2025-08-15 Lei Jiang , Shuzhou Sun , Biqing Qi , Yuchen Fu , Xiaohua Xu , Yuqiang Li , Dongzhan Zhou , Tianfan Fu

Accurately measuring protein-RNA binding affinity is crucial in many biological processes and drug design. Previous computational methods for protein-RNA binding affinity prediction rely on either sequence or structure features, unable to…

Biomolecules · Quantitative Biology 2025-01-06 Rong Han , Xiaohong Liu , Tong Pan , Jing Xu , Xiaoyu Wang , Wuyang Lan , Zhenyu Li , Zixuan Wang , Jiangning Song , Guangyu Wang , Ting Chen

Accurate prediction of drug-target binding affinity can accelerate drug discovery by prioritizing promising compounds before costly wet-lab screening. While deep learning has advanced this task, most models fuse ligand and protein…

Machine Learning · Computer Science 2025-09-26 Mohammadsaleh Refahi , Bahrad A. Sokhansanj , James R. Brown , Gail Rosen

Large language models (LLMs) have demonstrated their instruction-following capabilities and achieved powerful performance on various tasks. Inspired by their success, recent works in the molecular domain have led to the development of large…

Artificial Intelligence · Computer Science 2026-01-21 Jinyoung Park , Minseong Bae , Jeehye Na , Hyunwoo J. Kim

Revolutionizing drug discovery demands more than just understanding molecular interactions - it requires generative models that can design novel ligands tailored to specific biological targets. While chemical Language Models (cLMs) have…

Structure-based drug discovery faces the dual challenge of accurately capturing 3D protein-ligand interactions while navigating ultra-large chemical spaces to identify synthetically accessible candidates. In this work, we present a unified…

Machine Learning · Computer Science 2026-04-22 Carles Navarro , Philipp Tholke , Gianni de Fabritiis

Predicting compound-protein affinity is critical for accelerating drug discovery. Recent progress made by machine learning focuses on accuracy but leaves much to be desired for interpretability. Through molecular contacts underlying…

Biomolecules · Quantitative Biology 2020-01-01 Mostafa Karimi , Di Wu , Zhangyang Wang , Yang Shen

In structure-based drug design, accurately estimating the binding affinity between a candidate ligand and its protein receptor is a central challenge. Recent advances in artificial intelligence, particularly deep learning, have demonstrated…

Biomolecules · Quantitative Biology 2025-09-18 Md Masud Rana , Farjana Tasnim Mukta , Duc D. Nguyen