Towards the virtual screening of BIK inhibitors with the homology-modeled protein structure

Induction of apoptosis in tumor cells through direct triggering of the Bcl-2 regulated intrinsic pathway by small molecules carries great potential to overcome the shortcomings of current anticancer therapies. The Bcl-2 family members are crucial regulators of apoptosis. The BIK protein, is an important member of the Bcl-2 family and an attractive drug target. Homology model of BIK was developed based on the crystal structures of appropriate template. We have employed structure-based virtual screening techniques using Glide 5.6 to identify lead like molecules from an in-house library. The database has yielded 345 hits, the top scoring 60 ligands were selected and a pharmacokinetic analysis (ADME) was performed. We have identified six ligands from the combined approach of virtual screening followed by ADME that can work against BIK.