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Rich data and powerful machine learning models allow us to design drugs for a specific protein target \textit{in silico}. Recently, the inclusion of 3D structures during targeted drug design shows superior performance to other target-free…

Biomolecules · Quantitative Biology 2023-03-08 Jiaqi Guan , Wesley Wei Qian , Xingang Peng , Yufeng Su , Jian Peng , Jianzhu Ma

Structure-based drug design (SBDD) faces a fundamental scaling fidelity dilemma: rich pocket-aware conditioning captures interaction geometry but can be costly, often scales quadratically ($O(L^2)$) or worse with protein length ($L$), while…

Machine Learning · Computer Science 2026-02-02 Samyak Sanghvi , Nishant Ranjan , Tarak Karmakar

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

In the field of Structure-based Drug Design (SBDD), deep learning-based generative models have achieved outstanding performance in terms of docking score. However, further study shows that the existing molecular generative methods and…

Biomolecules · Quantitative Biology 2024-03-21 Bowen Gao , Minsi Ren , Yuyan Ni , Yanwen Huang , Bo Qiang , Zhi-Ming Ma , Wei-Ying Ma , Yanyan Lan

Designing protein binders targeting specific sites, which requires to generate realistic and functional interaction patterns, is a fundamental challenge in drug discovery. Current structure-based generative models are limited in generating…

Machine Learning · Computer Science 2025-10-17 Zishen Zhang , Xiangzhe Kong , Wenbing Huang , Yang Liu

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

We study a fundamental problem in structure-based drug design -- generating molecules that bind to specific protein binding sites. While we have witnessed the great success of deep generative models in drug design, the existing methods are…

Biomolecules · Quantitative Biology 2022-11-15 Shitong Luo , Jiaqi Guan , Jianzhu Ma , Jian Peng

Structure-based drug design (SBDD) leverages the 3D structure of biomolecular targets to guide the creation of new therapeutic agents. Recent advances in generative models, including diffusion models and geometric deep learning, have…

Biomolecules · Quantitative Biology 2025-01-28 Ali Khodabandeh Yalabadi , Mehdi Yazdani-Jahromi , Ozlem Ozmen Garibay

Identifying drug-target interactions is essential for developing effective therapeutics. Binding affinity quantifies these interactions, and traditional approaches rely on computationally intensive 3D structural data. In contrast, language…

Quantitative Methods · Quantitative Biology 2024-11-08 Radheesh Sharma Meda , Amir Barati Farimani

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with…

Biomolecules · Quantitative Biology 2025-03-07 Xiangxin Zhou , Yi Xiao , Haowei Lin , Xinheng He , Jiaqi Guan , Yang Wang , Qiang Liu , Feng Zhou , Liang Wang , Jianzhu Ma

Protein function is often controlled by ligands that bias the direction of state transitions, such as agonists and antagonists, rather than stabilizing a single conformation. This is especially important for clinically relevant G…

Biomolecules · Quantitative Biology 2026-05-12 Hanqun Cao , Aastha Pal , Sophia Tang , Yinuo Zhang , Jingjie Zhang , Pheng Ann Heng , Pranam Chatterjee

Accurate prediction of protein-ligand binding affinities is crucial for drug development. Recent advances in machine learning show promising results on this task. However, these methods typically rely heavily on labeled data, which can be…

Machine Learning · Computer Science 2024-06-13 Meng Liu , Saee Gopal Paliwal

Computational models that accurately predict the binding affinity of an input protein-chemical pair can accelerate drug discovery studies. These models are trained on available protein-chemical interaction datasets, which may contain…

Quantitative Methods · Quantitative Biology 2023-01-10 Rıza Özçelik , Alperen Bağ , Berk Atıl , Melih Barsbey , Arzucan Özgür , Elif Özkırımlı

Motivation: Prediction of the interaction affinity between proteins and compounds is a major challenge in the drug discovery process. WideDTA is a deep-learning based prediction model that employs chemical and biological textual sequence…

Quantitative Methods · Quantitative Biology 2019-02-13 Hakime Öztürk , Elif Ozkirimli , Arzucan Özgür

Diffusion models have demonstrated empirical successes in various applications and can be adapted to task-specific needs via guidance. This paper studies a form of gradient guidance for adapting a pre-trained diffusion model towards…

Machine Learning · Statistics 2024-10-17 Yingqing Guo , Hui Yuan , Yukang Yang , Minshuo Chen , Mengdi Wang

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

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit…

Biomolecules · Quantitative Biology 2026-05-28 Chen Wei , Fanding Xu , Minghao Sun , Zhiyuan Liu , Lin Wang , Tianrui Jia , Yihang Zhou , Yang Zhang

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

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

Structure based ligand discovery is one of the most successful approaches for augmenting the drug discovery process. Currently, there is a notable shift towards machine learning (ML) methodologies to aid such procedures. Deep learning has…

Machine Learning · Statistics 2018-06-12 Marta M. Stepniewska-Dziubinska , Piotr Zielenkiewicz , Pawel Siedlecki