AffinityVAE: A multi-objective model for protein-ligand affinity prediction and drug design

In the prediction of protein-ligand affinity, the traditional methods require a large amount of computing resources, and have certain limitations in predicting and simulating the structural changes. Although employing data-driven approaches can yield favorable outcomes in deep learning, it entails a lack of interpretability. Some methods may require additional structural information or domain knowledge to support the interpretation, which may limit their applicability. This paper proposes an affinity variational autoencoder (AffinityVAE) using interaction feature mapping and a variational autoencoder, which consists of a multi-objective model capable of end-to-end affinity prediction and drug discovery. In this study, the limitations of affinity prediction in terms of interpretability are tackled by proposing the concept of a protein-ligand interaction feature map. This increases the diversity and quantity of protein-ligand binding data by designing an adaptive autoencoder of target chemical properties to generate new ligands similar to known ligands and adding them to the original training set. AffinityVAE is then retrained using this extended training set to further validate the protein-ligand binding affinity prediction. Comparisons were conducted between the AffinityVAE and recent methods to demonstrate the high efficiency of the proposed model. The experimental results show that AffinityVAE has very high prediction performance, and it has the potential to enhance the diversity and the amount of protein-ligand binding data, which promotes the drug development.