Application of Deep Learning to Predict the Persistence, Bioaccumulation, and Toxicity of Pharmaceuticals.

Journal: Journal of chemical information and modeling
Published Date:

Abstract

This study investigates the application of a deep learning (DL) model, specifically a message-passing neural network (MPNN) implemented through Chemprop, to predict the persistence, bioaccumulation, and toxicity (PBT) characteristics of compounds, with a focus on pharmaceuticals. We employed a clustering strategy to provide a fair assessment of the model performances. By applying the generated model to a set of pharmaceutically relevant molecules, we aim to highlight potential PBT chemicals and extract PBT-relevant substructures. These substructures can serve as structural flags, alerting drug designers to potential environmental issues from the earliest stages of the drug discovery process. Incorporating these findings into pharmaceutical development workflows is expected to drive significant advancements in creating more environmentally friendly drug candidates while preserving their therapeutic efficacy.

Authors

  • Dominga Evangelista
    Department of Pharmacy and Biotechnology, Alma Mater Studiorum─University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
  • Elliot Nelson
    OMass Therapeutics, Building 4000, Chancellor Court, John Smith Dr, Oxford Business Park, ARC, Oxford OX4 2GX, United Kingdom.
  • Rachael Skyner
    OMass Therapeutics, Building 4000, Chancellor Court, John Smith Dr, Oxford Business Park, ARC, Oxford OX4 2GX, United Kingdom.
  • Ben Tehan
    OMass Therapeutics, Building 4000, Chancellor Court, John Smith Dr, Oxford Business Park, ARC, Oxford OX4 2GX, United Kingdom.
  • Mattia Bernetti
    Department of Biomolecular Sciences, University of Urbino, Urbino 60129, Italy.
  • Marinella Roberti
    Department of Pharmacy and Biotechnology, Alma Mater Studiorum─University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
  • Maria Laura Bolognesi
    Department of Pharmacy and Biotechnology, Alma Mater Studiorum─University of Bologna, Via Belmeloro 6, Bologna 40126, Italy.
  • Giovanni Bottegoni
    CompuNet, Istituto Italiano di Tecnologia, via Morego 30, 16163 Genova, Italy.