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The accurate screening of candidate drug ligands against target proteins through computational approaches is of prime interest to drug development efforts. Such virtual screening depends in part on methods to predict the binding affinity…

Machine Learning · Computer Science 2024-10-22 Ho-Joon Lee , Prashant S. Emani , Mark B. Gerstein

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…

Metric learning plays a critical role in training image retrieval and classification. It is also a key algorithm in representation learning, e.g., for feature learning and its alignment in metric space. Hyperbolic embedding has been…

Computer Vision and Pattern Recognition · Computer Science 2023-10-24 Shiyang Yan , Zongxuan Liu , Lin Xu

Predicting protein-ligand binding affinity remains intractable for multi-domain proteins, where inter-domain dynamics govern molecular recognition. Existing geometric deep learning methods typically treat proteins as monolithic static…

Machine Learning · Computer Science 2026-05-20 Shuo Zhang , Rongqi Hong , Huifeng Zhang , Jian K. Liu

Protein-ligand binding complexes are ubiquitous and essential to life. Protein-ligand binding affinity prediction (PLA) quantifies the binding strength between ligands and proteins, providing crucial insights for discovering and designing…

Computational Engineering, Finance, and Science · Computer Science 2025-04-24 Krinos Li , Xianglu Xiao , Zijun Zhong , Guang Yang

Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering.…

Biomolecules · Quantitative Biology 2022-06-07 Hannes Stärk , Octavian-Eugen Ganea , Lagnajit Pattanaik , Regina Barzilay , Tommi Jaakkola

Binding affinity optimization is crucial in early-stage drug discovery. While numerous machine learning methods exist for predicting ligand potency, their comparative efficacy remains unclear. This study evaluates the performance of…

Biomolecules · Quantitative Biology 2024-07-30 Nikolai Schapin , Carles Navarro , Albert Bou , Gianni De Fabritiis

Learning good image representations that are beneficial to downstream tasks is a challenging task in computer vision. As such, a wide variety of self-supervised learning approaches have been proposed. Among them, contrastive learning has…

Computer Vision and Pattern Recognition · Computer Science 2023-02-06 Yun Yue , Fangzhou Lin , Kazunori D Yamada , Ziming Zhang

Powerful generative AI models of protein-ligand structure have recently been proposed, but few of these methods support both flexible protein-ligand docking and affinity estimation. Of those that do, none can directly model multiple binding…

Machine Learning · Computer Science 2025-03-25 Alex Morehead , Jianlin Cheng

Due to its geometric properties, hyperbolic space can support high-fidelity embeddings of tree- and graph-structured data, upon which various hyperbolic networks have been developed. Existing hyperbolic networks encode geometric priors not…

Machine Learning · Computer Science 2023-03-14 Tao Yu , Christopher De Sa

Metric learning aims to learn a highly discriminative model encouraging the embeddings of similar classes to be close in the chosen metrics and pushed apart for dissimilar ones. The common recipe is to use an encoder to extract embeddings…

Computer Vision and Pattern Recognition · Computer Science 2022-03-23 Aleksandr Ermolov , Leyla Mirvakhabova , Valentin Khrulkov , Nicu Sebe , Ivan Oseledets

Embedding geometry plays a fundamental role in retrieval quality, yet dense retrievers for retrieval-augmented generation (RAG) remain largely confined to Euclidean space. However, natural language exhibits hierarchical structure from broad…

Information Retrieval · Computer Science 2026-02-10 Hiren Madhu , Ngoc Bui , Ali Maatouk , Leandros Tassiulas , Smita Krishnaswamy , Menglin Yang , Sukanta Ganguly , Kiran Srinivasan , Rex Ying

Accurately predicting the binding conformation of small-molecule ligands to protein targets is a critical step in rational drug design. Although recent deep learning-based docking surpasses traditional methods in speed and accuracy, many…

Computer Vision and Pattern Recognition · Computer Science 2025-08-14 Liyan Jia , Chuan-Xian Ren , Hong Yan

Applying deep learning concepts from image detection and graph theory has greatly advanced protein-ligand binding affinity prediction, a challenge with enormous ramifications for both drug discovery and protein engineering. We build upon…

Biomolecules · Quantitative Biology 2023-12-05 Gregory W. Kyro , Rafael I. Brent , Victor S. Batista

Predicting a ligand's bound pose to a target protein is a key component of early-stage computational drug discovery. Recent developments in machine learning methods have focused on improving pose quality at the cost of model runtime. For…

Biomolecules · Quantitative Biology 2024-10-23 Wojtek Treyde , Seohyun Chris Kim , Nazim Bouatta , Mohammed AlQuraishi

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

Publicly available collections of drug-like molecules have grown to comprise 10s of billions of possibilities in recent history due to advances in chemical synthesis. Traditional methods for identifying "hit" molecules from a large…

Predicting accurate protein-ligand binding affinity is important in drug discovery but remains a challenge even with computationally expensive biophysics-based energy scoring methods and state-of-the-art deep learning approaches. Despite…

Protein (receptor)--ligand interaction prediction is a critical component in computer-aided drug design, significantly influencing molecular docking and virtual screening processes. Despite the development of numerous scoring functions in…

Biomolecules · Quantitative Biology 2024-01-22 Haoyu Lin , Shiwei Wang , Jintao Zhu , Yibo Li , Jianfeng Pei , Luhua Lai

Embedding into hyperbolic space is emerging as an effective representation technique for datasets that exhibit hierarchical structure. This development motivates the need for algorithms that are able to effectively extract knowledge and…

Data Structures and Algorithms · Computer Science 2020-09-03 Xian Wu , Moses Charikar
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