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

arXiv: https://arxiv.org/abs/2509.13476 · HTML: https://mlsanity.com/paper/2509.13476/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 8 of its 45 references that are in the map.
- First posted on arXiv 15 Sep 2025.

## Builds on (most cited first, 8 of 8)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Effective Approaches to Attention-based Neural Machine Translation](https://mlsanity.com/paper/1508.04025/) (2015)
- [DeepDTA: Deep Drug-Target Binding Affinity Prediction](https://mlsanity.com/paper/1801.10193/) (2018)
- [Development and evaluation of a deep learning model for protein-ligand binding affinity prediction](https://mlsanity.com/paper/1712.07042/) (2017)
- [Improved Protein-ligand Binding Affinity Prediction with Structure-Based Deep Fusion Inference](https://mlsanity.com/paper/2005.07704/) (2020)
- [Deep learning for drug repurposing: methods, databases, and applications](https://mlsanity.com/paper/2202.05145/) (2022)
- [Geometric Graph Learning with Extended Atom-Types Features for Protein-Ligand Binding Affinity Prediction](https://mlsanity.com/paper/2301.06194/) (2023)
- [DynamicDTA: Drug-Target Binding Affinity Prediction Using Dynamic Descriptors and Graph Representation](https://mlsanity.com/paper/2505.11529/) (2025)

## Abstract (arXiv)

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.