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Molecular docking plays a crucial role in predicting the binding mode of ligands to target proteins, and covalent interactions, which involve the formation of a covalent bond between the ligand and the target, are particularly valuable due…

Biomolecules · Quantitative Biology 2025-06-27 Yangzhe Peng , Kaiyuan Gao , Liang He , Yuheng Cong , Haiguang Liu , Kun He , Lijun Wu

Compound-Protein Interaction (CPI) prediction aims to predict the pattern and strength of compound-protein interactions for rational drug discovery. Existing deep learning-based methods utilize only the single modality of protein sequences…

Biomolecules · Quantitative Biology 2024-02-14 Lirong Wu , Yufei Huang , Cheng Tan , Zhangyang Gao , Bozhen Hu , Haitao Lin , Zicheng Liu , Stan Z. Li

Understanding the intricate interplay among sequence, structure, and function remains a fundamental challenge in proteomics. The sequence-structure-function paradigm posits that biological roles are governed by the tertiary geometric…

Biomolecules · Quantitative Biology 2026-05-14 Hongwang Xiao , Wenjun Lin , Xi Chen , Hui Wang , Kai Chen , Jiashan Li , Yuancheng Sun , Sicheng Dai , Boya Wu , Qiwei Ye

Predicting the 3D structure of a macromolecule, such as a protein or an RNA molecule, is ranked top among the most difficult and attractive problems in bioinformatics and computational biology. Its importance comes from the relationship…

Biomolecules · Quantitative Biology 2016-12-14 Zhiyong Wang

Protein design is a fundamental challenge in biotechnology, aiming to design novel sequences with specific functions within the vast space of possible proteins. Recent advances in deep generative models have enabled function-based protein…

Machine Learning · Computer Science 2025-10-15 Nuowei Liu , Jiahao Kuang , Yanting Liu , Tao Ji , Changzhi Sun , Man Lan , Yuanbin Wu

Breakthroughs in high-accuracy protein structure prediction, such as AlphaFold, have established receptor-based molecule design as a critical driver for rapid early-phase drug discovery. However, most approaches still struggle to balance…

Biomolecules · Quantitative Biology 2025-06-18 Dong Xu , Zhangfan Yang , Ka-chun Wong , Zexuan Zhu , Jiangqiang Li , Junkai Ji

Molecular knowledge resides within three different modalities of information sources: molecular structures, biomedical documents, and knowledge bases. Effective incorporation of molecular knowledge from these modalities holds paramount…

Biomolecules · Quantitative Biology 2023-07-24 Yizhen Luo , Kai Yang , Massimo Hong , Xing Yi Liu , Zaiqing Nie

Nuclear magnetic resonance (NMR) spectroscopy is one of the leading techniques for protein studies. The method features a number of properties, allowing to explain macromolecular interactions mechanistically and resolve structures with…

Quantitative Methods · Quantitative Biology 2018-08-03 Piotr Klukowski , Adam Gonczarek

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…

Drug discovery can be viewed as a combinatorial search over an immense chemical space, motivating the development of deep generative models for de novo molecular design. Among these, GPT-based molecular language models (MLM) have shown…

Machine Learning · Computer Science 2026-02-02 Qianwei Yang , Dong Xu , Zhangfan Yang , Sisi Yuan , Zexuan Zhu , Jianqiang Li , Junkai Ji

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

The translation of comparative genomics into clinical decision support tools often depends on the quality of sequence alignments. However, currently used methods of multiple sequence alignments suffer from significant biases and problems…

Genomics · Quantitative Biology 2023-11-30 Manal Helal , Vitali Sintchenko

Drug repositioning aims to identify potential new indications for existing drugs to reduce the time and financial costs associated with developing new drugs. Most existing deep learning-based drug repositioning methods predominantly utilize…

Machine Learning · Computer Science 2025-06-02 Renye Zhang , Mengyun Yang , Qichang Zhao , Jianxin Wang

Self-supervised pretraining on molecular graphs has emerged as a promising approach for molecular property prediction, yet most existing methods operate at a single structural granularity and treat bond information as auxiliary edge…

Machine Learning · Computer Science 2026-05-18 Xiayu Liu , Zhengyi Lu , Hou-biao Li

Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration…

Information on the structure of molecules, retrieved via biochemical databases, plays a pivotal role in various disciplines, such as metabolomics, systems biology, and drug discovery. However, no such database can be complete, and the…

Biomolecules · Quantitative Biology 2023-08-25 Casper Asbjørn Eriksen , Jakob Lykke Andersen , Rolf Fagerberg , Daniel Merkle

Understanding molecular structure and related knowledge is crucial for scientific research. Recent studies integrate molecular graphs with their textual descriptions to enhance molecular representation learning. However, they focus on the…

Artificial Intelligence · Computer Science 2025-06-02 Yibo Li , Yuan Fang , Mengmei Zhang , Chuan Shi

Identification of high affinity drug-target interactions is a major research question in drug discovery. Proteins are generally represented by their structures or sequences. However, structures are available only for a small subset of…

Machine Learning · Computer Science 2020-12-22 Rıza Özçelik , Hakime Öztürk , Arzucan Özgür , Elif Ozkirimli

Recently, artificial intelligence for drug discovery has raised increasing interest in both machine learning and chemistry domains. The fundamental building block for drug discovery is molecule geometry and thus, the molecule's geometrical…

Machine Learning · Computer Science 2023-12-07 Weitao Du , Jiujiu Chen , Xuecang Zhang , Zhiming Ma , Shengchao Liu

Diffusion models offer a powerful means of capturing the manifold of realistic protein structures, enabling rapid design for protein engineering tasks. However, existing approaches observe critical failure modes when precise constraints are…

Biomolecules · Quantitative Biology 2026-03-27 Jacob K. Christopher , Austin Seamann , Jingyi Cui , Sagar Khare , Ferdinando Fioretto