Rapid Identification of Potential Inhibitors of Bruton's Tyrosine Kinase (BTK) by Structure-based Virtual Screening

Bruton's Tyrosine Kinase (BTK) is one of the non-receptor intracellular kinases expressing mainly in B cells and it regulates cell proliferation, apoptosis, and several cellular activities. Abnormal BTK activation is known to play a pivotal role in B cell malignant tumors. Herein, we used computer-aided drug design (CADD) to discover potential inhibitors against the BTK protein. By first acquiring ligand resources from the SPECS library, the ligand preparation and protein preparation on schrödinger were performed. Then the multi-stage docking from high-throughput virtual screening to extra precision were processed through virtual screening workflow. Subsequently, the interaction between the top four satisfied compounds with high docking scores and the BTK protein were analyzed based on results of multi-stage docking and comprehensive details were also discussed accordingly. This paper might lay a foundation for the following study in designing small molecules targeted B cell malignant tumors.