A Geometric Graph-Based Deep Learning Model for Drug-Target Affinity Prediction

Fuente: arXiv
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Autores principales: Rana, Md Masud, Mukta, Farjana Tasnim, Nguyen, Duc D.
Formato: Preprint
Publicado: 2025
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author Rana, Md Masud
Mukta, Farjana Tasnim
Nguyen, Duc D.
author_facet Rana, Md Masud
Mukta, Farjana Tasnim
Nguyen, Duc D.
contents 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 superior performance over traditional empirical and physics-based methods for this task, enabled by the growing availability of structural and experimental affinity data. In this work, we introduce DeepGGL, a deep convolutional neural network that integrates residual connections and an attention mechanism within a geometric graph learning framework. By leveraging multiscale weighted colored bipartite subgraphs, DeepGGL effectively captures fine-grained atom-level interactions in protein-ligand complexes across multiple scales. We benchmarked DeepGGL against established models on CASF-2013 and CASF-2016, where it achieved state-of-the-art performance with significant improvements across diverse evaluation metrics. To further assess robustness and generalization, we tested the model on the CSAR-NRC-HiQ dataset and the PDBbind v2019 holdout set. DeepGGL consistently maintained high predictive accuracy, highlighting its adaptability and reliability for binding affinity prediction in structure-based drug discovery.
format Preprint
id arxiv_https___arxiv_org_abs_2509_13476
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A Geometric Graph-Based Deep Learning Model for Drug-Target Affinity Prediction
Rana, Md Masud
Mukta, Farjana Tasnim
Nguyen, Duc D.
Biomolecules
Machine Learning
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 superior performance over traditional empirical and physics-based methods for this task, enabled by the growing availability of structural and experimental affinity data. In this work, we introduce DeepGGL, a deep convolutional neural network that integrates residual connections and an attention mechanism within a geometric graph learning framework. By leveraging multiscale weighted colored bipartite subgraphs, DeepGGL effectively captures fine-grained atom-level interactions in protein-ligand complexes across multiple scales. We benchmarked DeepGGL against established models on CASF-2013 and CASF-2016, where it achieved state-of-the-art performance with significant improvements across diverse evaluation metrics. To further assess robustness and generalization, we tested the model on the CSAR-NRC-HiQ dataset and the PDBbind v2019 holdout set. DeepGGL consistently maintained high predictive accuracy, highlighting its adaptability and reliability for binding affinity prediction in structure-based drug discovery.
title A Geometric Graph-Based Deep Learning Model for Drug-Target Affinity Prediction
topic Biomolecules
Machine Learning
url https://arxiv.org/abs/2509.13476