Hepatocellular carcinoma cells have high levels of the acidic ferritin H subunit, and targeted degradation of the H subunit is expected to induce iron overload triggering Ferroptosis in hepatocellular carcinoma cells. Our project aims to predict the drugable sites of H subunit by DoGSite algorithm, virtually dock small molecules with different binding sites and evaluate their binding activity by FlexX algorithm, so as to discover small molecule ligands that can bind specifically to ferritin H subunit and assemble them into PROTACs to target degradation of H subunit and induce Ferroptosis in hepatocellular carcinoma cells. 1. no small molecule ligands for ferritin H subunit have been reported. 2. all five binding pockets predicted by the DoGSite algorithm will undergo molecular docking. 3. molecules with better molecular docking results will be subjected to in vitro experiments to verify their binding activity and selectivity.
Ai intends to achieve the following milestones:
- Obtaining specific high-affinity small molecule ligand libraries for each binding pocket of the H subunit by virtual screening
- Obtain small molecule entity libraries by purchase or organic synthesis and perform preliminary in vitro experiments
- In vitro experiments resulted in the assembly of better active molecules into PROTACs for targeted degradation experiments