LigVoxel: inpainting binding pockets using 3D-convolutional neural networks.

Journal: Bioinformatics (Oxford, England)
Published Date:

Abstract

MOTIVATION: Structure-based drug discovery methods exploit protein structural information to design small molecules binding to given protein pockets. This work proposes a purely data driven, structure-based approach for imaging ligands as spatial fields in target protein pockets. We use an end-to-end deep learning framework trained on experimental protein-ligand complexes with the intention of mimicking a chemist's intuition at manually placing atoms when designing a new compound. We show that these models can generate spatial images of ligand chemical properties like occupancy, aromaticity and donor-acceptor matching the protein pocket.

Authors

  • Miha Škalič
    Computational Biophysics Laboratory, Universitat Pompeu Fabra , Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader 88, Barcelona 08003, Spain.
  • Alejandro Varela-Rial
    Acellera, Barcelona Biomedical Research Park (PRBB), Doctor Aiguader 88, Barcelona, Spain.
  • José Jiménez
    Computational Biophysics Laboratory, Universitat Pompeu Fabra , Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader 88, Barcelona 08003, Spain.
  • Gerard Martínez-Rosell
    Acellera , Carrer del Dr Trueta, 183 , 08005 Barcelona , Spain.
  • 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.