• MaSIF-neosurf can design binders for protein-ligand complexes, targeting neosurfaces (i.e., ligand-induced structural changes on the protein surface)
• Benchmark MaSIF-neosurf against RFAA on 14 ligand-induced PPI complexes with 8,907 decoys from PDBBind
• Use MaSIF-search to predict buried surfaces and identify complementary surface fingerprints from a database of protein fragments (~640,000)
• Construct full-length proteins with binding motifs and refining structures using the Rosetta FastDesign protocol and grafting (with a potential round of LigandMPNN optimization)
• Engineer and validate binders for Bcl2–venetoclax, DB3–progesterone, and PDF1–actinonin through experimental testing