Discovery and Characterization of Novel Receptor-Interacting Protein Kinase 1 Inhibitors Using Deep Learning and Virtual Screening

) of 6.77 μM for compound 24 and 68.70 μM for compound 41. Finally, molecular dynamics simulations and binding free energy calculations were conducted to elucidate the molecular mechanism of compounds 24 and 41 binding to RIPK1. The results show that Met92, Met95, Ala155, and Asp156 are key residues for novel RIPK1 inhibitors. In summary, this work discovered two hit compounds targeting RIPK1, which can be further structurally modified to become promising lead compounds.