Identification of potential inhibitors for Bruton’s Tyrosine Kinase (BTK) based on pharmacophore-based virtual screening

Abstract

Bruton’s tyrosine kinase (BTK) is well known for its role in the development, differentiation and proliferation of B-lineage cells. The dysregulation of BTK is closely related with the immunological disorders and BTK targeting is commonly studied in the treatment of immunological disorders. Here pharmacophore model was developed, and screening against ZINC database retrieved 1337 hit molecules of potential BTK inhibitors. Molecular docking was performed for all molecules and analysis on the top docked molecules revealed that the ligands interacted well in the binding pocket of BTK. A 100-ns molecular dynamics simulation confirmed the docked pose of ligand, while the calculation of binding free energy indicated that the hit molecule has comparable affinity with native ligand of BTK (2V3).