Combined pharmacophore, virtual screening and molecular dynamics studies to identify Bruton’s tyrosine kinase inhibitors

Abstract

Bruton’s tyrosine Kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase expressed in hematopoietic cells. BTK plays a critical role in many cellular signalling pathways making it a potential target to treat autoimmune diseases and cancer. BTK signalling is important for the production of arthritis-associated antibodies, and inhibiting BTK will help the system to block the production of disease-associated antibodies. In this study, we have implemented ligand-based pharmacophore modelling and virtual screening against natural compounds followed by molecular docking, density functional theory and molecular dynamics studies for 50 ns. Four compounds with high affinity towards BTK were identified, and it could be used as a potent lead molecule for designing BTK inhibitor.