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The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with…

Biomolecules · Quantitative Biology 2019-12-04 Yanjun Li , Mohammad A. Rezaei , Chenglong Li , Xiaolin Li , Dapeng Wu

Pre-trained models have been successful in many protein engineering tasks. Most notably, sequence-based models have achieved state-of-the-art performance on protein fitness prediction while structure-based models have been used…

Machine Learning · Computer Science 2023-07-25 Antonia Boca , Simon Mathis

Accurate drug target affinity prediction can improve drug candidate selection, accelerate the drug discovery process, and reduce drug production costs. Previous work focused on traditional fingerprints or used features extracted based on…

Machine Learning · Computer Science 2024-07-16 Amritpal Singh

Geometric Graph Neural Networks (GNNs) and Transformers have become state-of-the-art for learning from 3D protein structures. However, their reliance on message passing prevents them from capturing the hierarchical interactions that govern…

Machine Learning · Computer Science 2025-12-09 Chang Liu , Vivian Li , Linus Leong , Vladimir Radenkovic , Pietro Liò , Chaitanya K. Joshi

The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

Prediction of protein-ligand complexes for flexible proteins remains still a challenging problem in computational structural biology and drug design. Here we present two novel deep neural network approaches with significant improvement in…

Biomolecules · Quantitative Biology 2020-08-28 Amr H. Mahmoud , Jonas F. Lill , Markus A. Lill

Accurately predicting the binding affinity between drugs and proteins is an essential step for computational drug discovery. Since graph neural networks (GNNs) have demonstrated remarkable success in various graph-related tasks, GNNs have…

Quantitative Methods · Quantitative Biology 2020-12-18 Jingbo Zhou , Shuangli Li , Liang Huang , Haoyi Xiong , Fan Wang , Tong Xu , Hui Xiong , Dejing Dou

The field of geometric deep learning has had a profound impact on the development of innovative and powerful graph neural network architectures. Disciplines such as computer vision and computational biology have benefited significantly from…

Machine Learning · Computer Science 2023-04-28 Alex Morehead , Jianlin Cheng

Recent advances in computational modelling of atomic systems, spanning molecules, proteins, and materials, represent them as geometric graphs with atoms embedded as nodes in 3D Euclidean space. In these graphs, the geometric attributes…

The accurate prediction of protein-ligand binding affinity is important for drug discovery yet remains challenging for multi-domain proteins, where inter-domain dynamics and flexible linkers govern molecular recognition. Current geometric…

Quantitative Methods · Quantitative Biology 2026-01-27 Shuo Zhang , Jian K. Liu

Graph neural networks (GNN) have been shown to provide substantial performance improvements for atomistic material representation and modeling compared with descriptor-based machine learning models. While most existing GNN models for…

Materials Science · Physics 2022-04-08 Kamal Choudhary , Brian DeCost

Accurate prediction of drug-target interaction (DTI) is essential for in silico drug design. For the purpose, we propose a novel approach for predicting DTI using a GNN that directly incorporates the 3D structure of a protein-ligand…

Machine Learning · Computer Science 2019-04-18 Jaechang Lim , Seongok Ryu , Kyubyong Park , Yo Joong Choe , Jiyeon Ham , Woo Youn Kim

In this study, we tackle the challenging task of predicting secondary structures from protein primary sequences, a pivotal initial stride towards predicting tertiary structures, while yielding crucial insights into protein activity,…

Machine Learning · Computer Science 2025-11-18 Disha Varshney , Samarth Garg , Sarthak Tyagi , Deeksha Varshney , Nayan Deep , Asif Ekbal

Given native 2D contact map, protein 3D structure could be reconstructed with accuracy of 2A or better, and such reconstruction is a feasible computational approach for protein folding problem. The prediction accuracy from traditional…

Biomolecules · Quantitative Biology 2019-06-12 Yuhong Wang , Wei Li , Hongmao Sun , Kennie Cruz-Gutierrez

Graph Neural Networks (GNNs) have been widely used for various learning tasks, ranging from node classification to link prediction. They have demonstrated excellent performance in multiple domains involving graph-structured data. However,…

Machine Learning · Computer Science 2026-03-19 Steven E. Wilson , Sina Khanmohammadi

Proteins in complex with small molecule ligands represent the core of structure-based drug discovery. However, three-dimensional representations are absent from most deep-learning-based generative models. We here present a graph-based…

Biomolecules · Quantitative Biology 2022-04-07 Seung-gu Kang , Jeffrey K. Weber , Joseph A. Morrone , Leili Zhang , Tien Huynh , Wendy D. Cornell

The identification of cancer genes is a critical yet challenging problem in cancer genomics research. Existing computational methods, including deep graph neural networks, fail to exploit the multilayered gene-gene interactions or provide…

Machine Learning · Computer Science 2023-05-04 Michail Chatzianastasis , Michalis Vazirgiannis , Zijun Zhang

Prediction of ligand binding sites of proteins is a fundamental and important task for understanding the function of proteins and screening potential drugs. Most existing methods require experimentally determined protein holo-structures as…

Quantitative Methods · Quantitative Biology 2023-12-07 Shuo Zhang , Lei Xie

Prediction of protein-ligand (PL) binding affinity remains the key to drug discovery. Popular approaches in recent years involve graph neural networks (GNNs), which are used to learn the topology and geometry of PL complexes. However, GNNs…

Machine Learning · Computer Science 2022-05-17 Dmitrii Gavrilev , Nurlybek Amangeldiuly , Sergei Ivanov , Evgeny Burnaev

Equivariant Graph Neural Networks (eGNNs) trained on density-functional theory (DFT) data can potentially perform electronic structure prediction at unprecedented scales, enabling investigation of the electronic properties of materials with…

Machine Learning · Computer Science 2025-07-08 Manasa Kaniselvan , Alexander Maeder , Chen Hao Xia , Alexandros Nikolaos Ziogas , Mathieu Luisier