Bayesian machine learning to discover Bruton's tyrosine kinase inhibitors

Bruton's tyrosine kinase (BTK) has a crucial role in multiple cell signaling pathways including B-cell antigen receptor (BCR) and Fc receptor (FcR) signaling cascades, which has attracted much attention to find BTK inhibitors to treat autoimmune diseases. In this work, we constructed a Bayesian classification model for virtually seeking novel BTK inhibitors, which showed good performance in terms of screening efficiency and accuracy. Through searching for several chemical libraries including Chembl_17 (1,317,484 compounds), Chembridge (103,473 compounds), and Chemdiv (700,000 compounds) using this model followed by molecular docking and activity prediction, 52 compounds with novel scaffolds were acknowledged as potential BTK inhibitors, which could be promising starting points for further exploration. This study also provided a guide to construct an efficient and effective protocol for virtual screening by integrating machine learning methods.