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

Journal: Journal of chemical information and modeling
Published Date:

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, 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 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.

Authors

  • Alejandro Varela-Rial
    Acellera, Barcelona Biomedical Research Park (PRBB), Doctor Aiguader 88, Barcelona, Spain.
  • Iain Maryanow
    Acellera Labs, Doctor Trueta 183, 08005 Barcelona, Spain.
  • Maciej Majewski
    Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Carrer Dr. Aiguader 88, 08003 Barcelona, Spain.
  • Stefan Doerr
    Acellera Labs , C/Doctor Trueta 183 , 08005 Barcelona , Spain.
  • Nikolai Schapin
    Computational Science Laboratory, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), Carrer Dr. Aiguader 88, 08003 Barcelona, Spain.
  • José Jiménez-Luna
    Computational Science Laboratory , Parc de Recerca Biomèdica de Barcelona , Universitat Pompeu Fabra , C Dr Aiguader 88 , Barcelona , 08003 , Spain . Email: gianni.defabritiis@upf.edu.
  • Gianni De Fabritiis
    Computational Science Laboratory , Parc de Recerca Biomèdica de Barcelona , Universitat Pompeu Fabra , C Dr Aiguader 88 , Barcelona , 08003 , Spain . Email: gianni.defabritiis@upf.edu.