Role of death-associated protein kinase 1 (DAPK1) in retinal degenerative diseases: an approach towards therapeutic intervention.

The Death-associated protein kinase 1 () has emerged as a crucial player in the pathogenesis of degenerative diseases. As a serine/threonine kinase family member, regulates critical signaling pathways, such as apoptosis and autophagy. In this study, we comprehensively analyzed interactors and enriched molecular functions, biological processes, phenotypic expression, disease associations, and aging signatures to elucidate the molecular networks of . Furthermore, we employed a structure-based virtual screening approach using the PubChem database, which enabled the identification of potential bioactive compounds capable of inhibiting , including caspase inhibitors and synthetic analogs. Three selected compounds, CID24602687, CID8843795, and CID110869998, exhibited high docking affinity and selectivity towards DAPK1, which were further investigated using molecular dynamics simulations to understand their binding patterns. Our findings establish a connection between DAPK1 and retinal degenerative diseases and highlight the potential of these selected compounds for the development of novel therapeutic strategies. This study provides valuable insights into the molecular mechanisms underlying DAPK1-related diseases, and offers new opportunities for the discovery of effective treatments for retinal degeneration.Communicated by Ramaswamy H. Sarma.