Structure-Based Virtual Screening and Discovery of New Bi-functional DAPK1 Inhibitors

Recently, a new signaling complex Death-Associated Protein Kinase 1 (DAPK1)-N-methyl D-aspartate receptor subtype 2B (NR2B) engaged in the neuronal death cascade was identified where it was found that after stroke injury, N-methyl-D-aspartate glutamate (NMDA) receptors interact with DAPK1 through NR2B subunit and lead to excitotoxicity via overactivation of NMDA receptors. In this study, we used ZINC-12 database to find out potential inhibitor of DAPK1 and found some natural compounds showing good binding affinity towards DAPK1. These natural compounds showed interactions with ATP-binding site residues as well as substrate-recognition motifs. Thus, it has been concluded that the ligands those are showing interactions with both the sites could be considered as potential inhibitors for DAPK1.

Automated summary

Recently, a new signaling complex involving DAPK1 and NR2B was discovered to play a role in neuronal death cascade, where NMDA receptors interact with DAPK1 through NR2B subunit after stroke injury, leading to excitotoxicity. Using the ZINC-12 database, potential inhibitors of DAPK1 were identified, particularly natural compounds showing strong binding affinity with both ATP-binding site residues and substrate-recognition motifs. These findings suggest that these ligands have the potential to be inhibitors of DAPK1.