DeepSnap-Deep Learning Approach Predicts Progesterone Receptor Antagonist Activity With High Performance.

The progesterone receptor (PR) is important therapeutic target for many malignancies and endocrine disorders due to its role in controlling ovulation and pregnancy via the reproductive cycle. Therefore, the modulation of PR activity using its agonists and antagonists is receiving increasing interest as novel treatment strategy. However, clinical trials using the PR modulators have not yet been found conclusive evidences. Recently, increasing evidence from several fields shows that the classification of chemical compounds, including agonists and antagonists, can be done with recent improvements in deep learning (DL) using deep neural network. Therefore, we recently proposed a novel DL-based quantitative structure-activity relationship (QSAR) strategy using transfer learning to build prediction models for agonists and antagonists. By employing this novel approach, referred as DeepSnap-DL method, which uses images captured from 3-dimension (3D) chemical structure with multiple angles as input data into the DL classification, we constructed prediction models of the PR antagonists in this study. Here, the DeepSnap-DL method showed a high performance prediction of the PR antagonists by optimization of some parameters and image adjustment from 3D-structures. Furthermore, comparison of the prediction models from this approach with conventional machine learnings (MLs) indicated the DeepSnap-DL method outperformed these MLs. Therefore, the models predicted by DeepSnap-DL would be powerful tool for not only QSAR field in predicting physiological and agonist/antagonist activities, toxicity, and molecular bindings; but also for identifying biological or pathological phenomena.