PlayMolecule Glimpse: Understanding Protein–Ligand Property Predictions with Interpretable Neural Networks

Abstract

Deep learning has been successfully applied to structure-based protein-ligand affinity prediction, yet the black box nature of these models raises some questions. In a previous study, we presented K_DEEP, a convolutional neural network that predicted the binding affinity of a given protein-ligand complex while reaching state-of-the-art performance. However, it was unclear what this model was learning. In this work, we present a new application to visualize the contribution of each input atom to the prediction made by the convolutional neural network, aiding in the interpretability of such predictions. The results suggest that K_DEEP is able to learn meaningful chemistry signals from the data, but it has also exposed the inaccuracies of the current model, serving as a guideline for further optimization of our prediction tools.