HAC-Net: A Hybrid Attention-Based Convolutional Neural Network for Highly Accurate Protein-Ligand Binding Affinity Prediction

Applying deep learning concepts from image detection and graph theory has greatly advanced protein-ligand binding affinity prediction, a challenge with enormous ramifica-tions for both drug discovery and protein engineering. We build upon these advances by designing a novel deep learning architecture consisting of a 3-dimensional convolutional neural network utilizing channel-wise attention and two graph convolu-tional networks utilizing attention-based aggregation of node features. HAC-Net (Hybrid Attention-Based Convolutional Neural Network) obtains state-of-the-art results on the PDBbind v.2016 core set, the most widely recognized benchmark in the field. We extensively assess the generalizability of our model using multiple train-test splits, each of which maximizes differences between either protein structures, protein sequences, or ligand extended -connectivity fingerprints of complexes in the training and test sets. Furthermore, we perform 10-fold cross-validation with a similarity cutoff between SMILES strings of ligands in the training and test sets and also evaluate the performance of HAC-Net on lower -quality data. We envision that this model can be extended to a broad range of supervised learning problems related to structure -based biomolecular property prediction. All of our software is available as an open-source repository at https://github.com/gregory-kyro/HAC-Net/, and the HACNet Python package is available through PyPI.

Automated summary

Deep learning and graph theory have greatly advanced protein-ligand binding affinity prediction. This study introduces a novel deep learning architecture consisting of a 3D convolutional neural network and two graph convolutional networks. The model, HAC-Net, achieves state-of-the-art results on the PDBbind v.2016 core set.